Obesity

WASHINGTON — Glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications appear beneficial for people with systemic lupus erythematosus (SLE) and lupus nephritis, two new studies suggest. 

“The risk of cardiovascular disease is thought to be at least double that for people with lupus ... and we know the risk of progressing to end-stage renal disease [ESKD] for patients with lupus nephritis can be as high as 10%-30%, so there’s clearly a major unmet need for new treatments and approaches to improve these outcomes, perhaps with adjunctive treatment beyond our typical immunosuppressive therapy,” April Jorge, MD, of Massachusetts General Hospital, Boston, said at the annual meeting of the American College of Rheumatology (ACR). 

The GLP-1 RAs are approved for the treatment of type 2 diabetes (T2D) and obesity. They also have proven cardiovascular benefit, along with emerging data suggesting kidney protection independent of glucose lowering. Jorge presented findings from a study using data from the US multicenter electronic health record database TriNetX, showing that, among patients who had both T2D and SLE, those using GLP-1 RAs had lower risks for major adverse cardiac events (MACE), venous thrombosis, kidney disease progression, and all-cause mortality, compared with those using a different class of T2D medication. 

A second study using TriNetX, presented at the same ACR meeting session by Anna-Kay Palmer, MD, a third-year internal medicine resident at Jefferson Einstein Hospital, Philadelphia, Pennsylvania, showed that GLP-1 RAs reduced the risk of progression to ESKD in patients with lupus nephritis, possibly caused by reductions in pro-inflammatory mediators.

Asked to comment, session moderator Diane L. Kamen, MD, professor of medicine at the Medical University of South Carolina Division of Rheumatology, Charleston, said in an interview that she definitely supports the use of GLP-1 RAs for patients who have SLE and/or lupus nephritis and also a drug label indication, either T2D or obesity. “[The GLP-1 RA prescriber] will usually run it by rheumatology to make sure that it doesn’t conflict with any of their other medical treatment, and it’s very reassuring to know that they could actually get a win-win.” 

But as far as prescribing off-label for those with SLE/lupus nephritis who don’t have other GLP-1 RA indications, Kamen said, “that’s a black hole at this point. We need to do those prospective studies. But if they have another indication, yes.”

 

Cardiovascular, Kidney Benefits of GLP-1 RAs

Jorge noted that patients with lupus were excluded from the randomized clinical trials of GLP-1 RAs, so the current study was designed to investigate the potential impact of these medications on cardiovascular and kidney outcomes in patients with SLE and lupus nephritis. 

From TriNetX data for 46 healthcare organizations nationwide, a total of 96,511 patients with both SLE and T2D but not ESKD had initiated either a GLP-1 RA or another diabetes drug class, dipeptidyl peptidase 4 inhibitors (DPP4i), between October 2006 and August 2021. Of those, 29,177 had lupus nephritis. 

Propensity score matching for factors such as demographics, lupus severity, comorbidities, and medication use was used to emulate a randomized trial. This yielded 25,838 with SLE and T2D, of whom 910 initiated a GLP-1 RA and 1004 started a DPP4i, and 12,387 with lupus nephritis and T2D, including 267 on a GLP-1 RA and 324 on a DPP4i. After matching, the mean age was 55 years, more than 90% were women, and just under half were White individuals. About one third had chronic kidney disease stages ≥ 3, and about 15% had heart failure. 

Over an average follow-up time of 1.2-1.4 years among those with SLE, the hazard ratio (HR) for MACE (a composite of myocardial infarction, stroke, and heart failure) for those taking a GLP-1 RA vs a DPP4i was 0.66, a significant difference. And for venous thrombosis, the HR was also significant at 0.49.

Kidney disease progression, defined as an estimated glomerular filtration rate decline of 30% or more or new ESKD, was significantly less likely in the GLP-1 RA group, with a HR of 0.77. All-cause mortality also was dramatically reduced (HR, 0.26). As expected, there was no difference in control outcome, genital infections (HR, 1.02). 

In the subgroup with lupus nephritis, there were also lower risks for both MACE (HR, 0.64) and for renal progression (HR, 0.70). “The findings suggest similar cardiac and kidney benefits among patients with SLE and lupus nephritis as have been observed in other populations,” Jorge concluded. 

Kamen commented that the study design “was pretty brilliant, because you wouldn’t be able to do a placebo-controlled trial since the indication was diabetes ... but the fact is you do see that the GLP-1 RA gets the benefit whereas the other drug does not.”

Next steps, Jorge said, will be mechanistic studies to better understand the effects of GLP-1 RAs in lupus and other rheumatic diseases, prospective studies of GLP-1 RAs in SLE and lupus nephritis without diabetes, and clarification of ideal timing for GLP-1 RA use in SLE and lupus nephritis. 

“Ideally, with our prospective studies with these patients we can try to isolate the effect on patients with lupus and also better understand whether there might be an impact on disease activity through the anti-inflammatory effects of these medications, rather than just the cardioprotective and nephroprotective benefits,” she said. 

 

In Those With Lupus Nephritis, Kidney Protection Seen

In her presentation, Palmer noted that, despite immunosuppressive therapies for SLE, 10%-20% of patients who develop lupus nephritis will progress to ESKD within 5 years of diagnosis. 

She added that GLP-1 RAs have been shown to reduce albuminuria in people with diabetes and have been hypothesized to reduce inflammation through multiple pathways, thereby potentially reducing kidney disease independently of the presence of diabetes or weight loss. These pathways include modulating immune cell signaling and reducing pro-inflammatory cytokines. 

Based on all this, Palmer and colleagues used International Classification of Diseases – 10th edition diagnostic codes in TriNetX to identify 839 patients who had been diagnosed with lupus nephritis between 2014 and 2024 and who were prescribed liraglutide, dulaglutide, semaglutide, or exenatide for any time after the lupus nephritis diagnosis. Another 29,840 patients with lupus nephritis had not used GLP-1 RAs. 

After 1:1 propensity score matching for age, sex, race, ethnicity, presence of hypertension, diabetes, use of immunosuppressive and diabetes medication, smoking, obesity, and statin use, there were 735 individuals in each group. About two thirds in each had diabetes, whereas the rest had been prescribed the GLP-1 RAs for other indications. 

Patients who were not on GLP-1 RAs were twice as likely to develop ESKD or dialysis (8.88% vs 3.971%; odds ratio, 2.35; P = .001). 

Kamen pointed out that not including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was a study flaw. On the other hand, the fact that not everyone in this study had diabetes was an advantage.

Jorge received grant/research support from Bristol-Myers Squibb, Cabaletta Bio, and the Lupus Clinical Investigator Network. Kamen is an adviser/review panel member for Alpine Immune Sciences. Palmer had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications appear beneficial for people with systemic lupus erythematosus (SLE) and lupus nephritis, two new studies suggest. 

“The risk of cardiovascular disease is thought to be at least double that for people with lupus ... and we know the risk of progressing to end-stage renal disease [ESKD] for patients with lupus nephritis can be as high as 10%-30%, so there’s clearly a major unmet need for new treatments and approaches to improve these outcomes, perhaps with adjunctive treatment beyond our typical immunosuppressive therapy,” April Jorge, MD, of Massachusetts General Hospital, Boston, said at the annual meeting of the American College of Rheumatology (ACR). 

The GLP-1 RAs are approved for the treatment of type 2 diabetes (T2D) and obesity. They also have proven cardiovascular benefit, along with emerging data suggesting kidney protection independent of glucose lowering. Jorge presented findings from a study using data from the US multicenter electronic health record database TriNetX, showing that, among patients who had both T2D and SLE, those using GLP-1 RAs had lower risks for major adverse cardiac events (MACE), venous thrombosis, kidney disease progression, and all-cause mortality, compared with those using a different class of T2D medication. 

A second study using TriNetX, presented at the same ACR meeting session by Anna-Kay Palmer, MD, a third-year internal medicine resident at Jefferson Einstein Hospital, Philadelphia, Pennsylvania, showed that GLP-1 RAs reduced the risk of progression to ESKD in patients with lupus nephritis, possibly caused by reductions in pro-inflammatory mediators.

Asked to comment, session moderator Diane L. Kamen, MD, professor of medicine at the Medical University of South Carolina Division of Rheumatology, Charleston, said in an interview that she definitely supports the use of GLP-1 RAs for patients who have SLE and/or lupus nephritis and also a drug label indication, either T2D or obesity. “[The GLP-1 RA prescriber] will usually run it by rheumatology to make sure that it doesn’t conflict with any of their other medical treatment, and it’s very reassuring to know that they could actually get a win-win.” 

But as far as prescribing off-label for those with SLE/lupus nephritis who don’t have other GLP-1 RA indications, Kamen said, “that’s a black hole at this point. We need to do those prospective studies. But if they have another indication, yes.”

 

Cardiovascular, Kidney Benefits of GLP-1 RAs

Jorge noted that patients with lupus were excluded from the randomized clinical trials of GLP-1 RAs, so the current study was designed to investigate the potential impact of these medications on cardiovascular and kidney outcomes in patients with SLE and lupus nephritis. 

From TriNetX data for 46 healthcare organizations nationwide, a total of 96,511 patients with both SLE and T2D but not ESKD had initiated either a GLP-1 RA or another diabetes drug class, dipeptidyl peptidase 4 inhibitors (DPP4i), between October 2006 and August 2021. Of those, 29,177 had lupus nephritis. 

Propensity score matching for factors such as demographics, lupus severity, comorbidities, and medication use was used to emulate a randomized trial. This yielded 25,838 with SLE and T2D, of whom 910 initiated a GLP-1 RA and 1004 started a DPP4i, and 12,387 with lupus nephritis and T2D, including 267 on a GLP-1 RA and 324 on a DPP4i. After matching, the mean age was 55 years, more than 90% were women, and just under half were White individuals. About one third had chronic kidney disease stages ≥ 3, and about 15% had heart failure. 

Over an average follow-up time of 1.2-1.4 years among those with SLE, the hazard ratio (HR) for MACE (a composite of myocardial infarction, stroke, and heart failure) for those taking a GLP-1 RA vs a DPP4i was 0.66, a significant difference. And for venous thrombosis, the HR was also significant at 0.49.

Kidney disease progression, defined as an estimated glomerular filtration rate decline of 30% or more or new ESKD, was significantly less likely in the GLP-1 RA group, with a HR of 0.77. All-cause mortality also was dramatically reduced (HR, 0.26). As expected, there was no difference in control outcome, genital infections (HR, 1.02). 

In the subgroup with lupus nephritis, there were also lower risks for both MACE (HR, 0.64) and for renal progression (HR, 0.70). “The findings suggest similar cardiac and kidney benefits among patients with SLE and lupus nephritis as have been observed in other populations,” Jorge concluded. 

Kamen commented that the study design “was pretty brilliant, because you wouldn’t be able to do a placebo-controlled trial since the indication was diabetes ... but the fact is you do see that the GLP-1 RA gets the benefit whereas the other drug does not.”

Next steps, Jorge said, will be mechanistic studies to better understand the effects of GLP-1 RAs in lupus and other rheumatic diseases, prospective studies of GLP-1 RAs in SLE and lupus nephritis without diabetes, and clarification of ideal timing for GLP-1 RA use in SLE and lupus nephritis. 

“Ideally, with our prospective studies with these patients we can try to isolate the effect on patients with lupus and also better understand whether there might be an impact on disease activity through the anti-inflammatory effects of these medications, rather than just the cardioprotective and nephroprotective benefits,” she said. 

 

In Those With Lupus Nephritis, Kidney Protection Seen

In her presentation, Palmer noted that, despite immunosuppressive therapies for SLE, 10%-20% of patients who develop lupus nephritis will progress to ESKD within 5 years of diagnosis. 

She added that GLP-1 RAs have been shown to reduce albuminuria in people with diabetes and have been hypothesized to reduce inflammation through multiple pathways, thereby potentially reducing kidney disease independently of the presence of diabetes or weight loss. These pathways include modulating immune cell signaling and reducing pro-inflammatory cytokines. 

Based on all this, Palmer and colleagues used International Classification of Diseases – 10th edition diagnostic codes in TriNetX to identify 839 patients who had been diagnosed with lupus nephritis between 2014 and 2024 and who were prescribed liraglutide, dulaglutide, semaglutide, or exenatide for any time after the lupus nephritis diagnosis. Another 29,840 patients with lupus nephritis had not used GLP-1 RAs. 

After 1:1 propensity score matching for age, sex, race, ethnicity, presence of hypertension, diabetes, use of immunosuppressive and diabetes medication, smoking, obesity, and statin use, there were 735 individuals in each group. About two thirds in each had diabetes, whereas the rest had been prescribed the GLP-1 RAs for other indications. 

Patients who were not on GLP-1 RAs were twice as likely to develop ESKD or dialysis (8.88% vs 3.971%; odds ratio, 2.35; P = .001). 

Kamen pointed out that not including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was a study flaw. On the other hand, the fact that not everyone in this study had diabetes was an advantage.

Jorge received grant/research support from Bristol-Myers Squibb, Cabaletta Bio, and the Lupus Clinical Investigator Network. Kamen is an adviser/review panel member for Alpine Immune Sciences. Palmer had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications appear beneficial for people with systemic lupus erythematosus (SLE) and lupus nephritis, two new studies suggest. 

“The risk of cardiovascular disease is thought to be at least double that for people with lupus ... and we know the risk of progressing to end-stage renal disease [ESKD] for patients with lupus nephritis can be as high as 10%-30%, so there’s clearly a major unmet need for new treatments and approaches to improve these outcomes, perhaps with adjunctive treatment beyond our typical immunosuppressive therapy,” April Jorge, MD, of Massachusetts General Hospital, Boston, said at the annual meeting of the American College of Rheumatology (ACR). 

The GLP-1 RAs are approved for the treatment of type 2 diabetes (T2D) and obesity. They also have proven cardiovascular benefit, along with emerging data suggesting kidney protection independent of glucose lowering. Jorge presented findings from a study using data from the US multicenter electronic health record database TriNetX, showing that, among patients who had both T2D and SLE, those using GLP-1 RAs had lower risks for major adverse cardiac events (MACE), venous thrombosis, kidney disease progression, and all-cause mortality, compared with those using a different class of T2D medication. 

A second study using TriNetX, presented at the same ACR meeting session by Anna-Kay Palmer, MD, a third-year internal medicine resident at Jefferson Einstein Hospital, Philadelphia, Pennsylvania, showed that GLP-1 RAs reduced the risk of progression to ESKD in patients with lupus nephritis, possibly caused by reductions in pro-inflammatory mediators.

Asked to comment, session moderator Diane L. Kamen, MD, professor of medicine at the Medical University of South Carolina Division of Rheumatology, Charleston, said in an interview that she definitely supports the use of GLP-1 RAs for patients who have SLE and/or lupus nephritis and also a drug label indication, either T2D or obesity. “[The GLP-1 RA prescriber] will usually run it by rheumatology to make sure that it doesn’t conflict with any of their other medical treatment, and it’s very reassuring to know that they could actually get a win-win.” 

But as far as prescribing off-label for those with SLE/lupus nephritis who don’t have other GLP-1 RA indications, Kamen said, “that’s a black hole at this point. We need to do those prospective studies. But if they have another indication, yes.”

 

Cardiovascular, Kidney Benefits of GLP-1 RAs

Jorge noted that patients with lupus were excluded from the randomized clinical trials of GLP-1 RAs, so the current study was designed to investigate the potential impact of these medications on cardiovascular and kidney outcomes in patients with SLE and lupus nephritis. 

From TriNetX data for 46 healthcare organizations nationwide, a total of 96,511 patients with both SLE and T2D but not ESKD had initiated either a GLP-1 RA or another diabetes drug class, dipeptidyl peptidase 4 inhibitors (DPP4i), between October 2006 and August 2021. Of those, 29,177 had lupus nephritis. 

Propensity score matching for factors such as demographics, lupus severity, comorbidities, and medication use was used to emulate a randomized trial. This yielded 25,838 with SLE and T2D, of whom 910 initiated a GLP-1 RA and 1004 started a DPP4i, and 12,387 with lupus nephritis and T2D, including 267 on a GLP-1 RA and 324 on a DPP4i. After matching, the mean age was 55 years, more than 90% were women, and just under half were White individuals. About one third had chronic kidney disease stages ≥ 3, and about 15% had heart failure. 

Over an average follow-up time of 1.2-1.4 years among those with SLE, the hazard ratio (HR) for MACE (a composite of myocardial infarction, stroke, and heart failure) for those taking a GLP-1 RA vs a DPP4i was 0.66, a significant difference. And for venous thrombosis, the HR was also significant at 0.49.

Kidney disease progression, defined as an estimated glomerular filtration rate decline of 30% or more or new ESKD, was significantly less likely in the GLP-1 RA group, with a HR of 0.77. All-cause mortality also was dramatically reduced (HR, 0.26). As expected, there was no difference in control outcome, genital infections (HR, 1.02). 

In the subgroup with lupus nephritis, there were also lower risks for both MACE (HR, 0.64) and for renal progression (HR, 0.70). “The findings suggest similar cardiac and kidney benefits among patients with SLE and lupus nephritis as have been observed in other populations,” Jorge concluded. 

Kamen commented that the study design “was pretty brilliant, because you wouldn’t be able to do a placebo-controlled trial since the indication was diabetes ... but the fact is you do see that the GLP-1 RA gets the benefit whereas the other drug does not.”

Next steps, Jorge said, will be mechanistic studies to better understand the effects of GLP-1 RAs in lupus and other rheumatic diseases, prospective studies of GLP-1 RAs in SLE and lupus nephritis without diabetes, and clarification of ideal timing for GLP-1 RA use in SLE and lupus nephritis. 

“Ideally, with our prospective studies with these patients we can try to isolate the effect on patients with lupus and also better understand whether there might be an impact on disease activity through the anti-inflammatory effects of these medications, rather than just the cardioprotective and nephroprotective benefits,” she said. 

 

In Those With Lupus Nephritis, Kidney Protection Seen

In her presentation, Palmer noted that, despite immunosuppressive therapies for SLE, 10%-20% of patients who develop lupus nephritis will progress to ESKD within 5 years of diagnosis. 

She added that GLP-1 RAs have been shown to reduce albuminuria in people with diabetes and have been hypothesized to reduce inflammation through multiple pathways, thereby potentially reducing kidney disease independently of the presence of diabetes or weight loss. These pathways include modulating immune cell signaling and reducing pro-inflammatory cytokines. 

Based on all this, Palmer and colleagues used International Classification of Diseases – 10th edition diagnostic codes in TriNetX to identify 839 patients who had been diagnosed with lupus nephritis between 2014 and 2024 and who were prescribed liraglutide, dulaglutide, semaglutide, or exenatide for any time after the lupus nephritis diagnosis. Another 29,840 patients with lupus nephritis had not used GLP-1 RAs. 

After 1:1 propensity score matching for age, sex, race, ethnicity, presence of hypertension, diabetes, use of immunosuppressive and diabetes medication, smoking, obesity, and statin use, there were 735 individuals in each group. About two thirds in each had diabetes, whereas the rest had been prescribed the GLP-1 RAs for other indications. 

Patients who were not on GLP-1 RAs were twice as likely to develop ESKD or dialysis (8.88% vs 3.971%; odds ratio, 2.35; P = .001). 

Kamen pointed out that not including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was a study flaw. On the other hand, the fact that not everyone in this study had diabetes was an advantage.

Jorge received grant/research support from Bristol-Myers Squibb, Cabaletta Bio, and the Lupus Clinical Investigator Network. Kamen is an adviser/review panel member for Alpine Immune Sciences. Palmer had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Up to one in seven young adults with obesity and type 2 diabetes (T2D) have clinically significant hepatic fibrosis, signaling the crucial need for screening in this population to aid early detection and intervention.

METHODOLOGY:

• Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
• Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
• All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
• Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.

TAKEAWAY:

• Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
• There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
• The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
• In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
• The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).

IN PRACTICE:

“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.

SOURCE:

This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.

LIMITATIONS:

The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.

DISCLOSURES:

This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Up to one in seven young adults with obesity and type 2 diabetes (T2D) have clinically significant hepatic fibrosis, signaling the crucial need for screening in this population to aid early detection and intervention.

METHODOLOGY:

• Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
• Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
• All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
• Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.

TAKEAWAY:

• Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
• There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
• The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
• In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
• The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).

IN PRACTICE:

“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.

SOURCE:

This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.

LIMITATIONS:

The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.

DISCLOSURES:

This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Up to one in seven young adults with obesity and type 2 diabetes (T2D) have clinically significant hepatic fibrosis, signaling the crucial need for screening in this population to aid early detection and intervention.

METHODOLOGY:

• Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
• Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
• All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
• Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.

TAKEAWAY:

• Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
• There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
• The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
• In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
• The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).

IN PRACTICE:

“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.

SOURCE:

This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.

LIMITATIONS:

The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.

DISCLOSURES:

This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

If we’ve learned anything about obesity prevention it’s that if we wait too long the die is cast and our success rate is nil. The GLP-1 antagonists seem to be a workable solution for treating the adult and adolescent population, but I have been afraid that their success will divert too much of our attention away from prevention.

Fortunately, there still seems to be a few researchers committed to the age group in which obesity could be headed off before our only option is treatment. In one recent study, “Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity,” researchers collected data from more than 28,000 children in 55 cohorts during the period from 1994 to 2023). The investigators found that residence in a low–food access, low-income neighborhoods during pregnancy and early childhood was associated with higher BMI “Z” scores, a higher risk of obesity, and severe obesity in childhood. The researchers defined low food access as living greater than 0.5 miles away from a grocery store in an urban setting or greater than 10 minutes away in a rural setting. I don’t think those associations should surprise us, but having some data from a large population may be valuable should we ever find the political will to undertake any steps toward prevention.

I found a Viewpoint article published 2 weeks earlier in the same journal, titled, “The Exposome as a Key to Understanding Pediatric Health Disparities.” I know what the “biome” is and have heard gastroenterologists expound on the power that billions of our little single-celled friends residing in our gut have on seemingly unrelated and spatially distant events in our body. But, “exposome” was a new word for me, although it turns out the concept is simple and one I had harbored since late childhood. 

 

The opening sentence of the article reads “One’s environment profoundly changes health outcomes throughout one’s lifespan.” That truism was obvious to my 7-year-old self as I observed my playmates who lived in a poorly kept house in the less desirable area two blocks away and didn’t eat breakfast and were sick more often than the rest of us more-fortunates.

The authors define the exposome as the “totality of an individual’s non-genetic exposures, including psychosocial experiences, structural social determinants, chemical pollution, and neighborhood infrastructure.” This seems to be a pretty complete description of the nurture side of the nature versus nurture conversation. 

I suspect that, like me, most of you through observation and intuition have included your own interpretation of the exposome in your professional activities. However, the authors feel we could be more robust in our efforts and claim that “current pediatric practice largely neglects to characterize health disparities in terms of salient environmental practices.” They go on to call for incorporation of an “exposome lens in pediatric research and healthcare delivery.”

I’m not sure this is a valid criticism. There is certainly more that could be done when it comes to research that examines the effect of environmental stressors. And, I suspect the authors would view this recent paper on the association between neighborhood food access as a step in the right direction. However, when it comes to healthcare delivery, at least at the level where the stethoscope meets the chest, I think, or at least hope, the authors are underestimating the observational skills and sensitivity of primary care providers.

We were all taught to take an appropriate medical history when evaluating a patient. And, through our formal education, our personal observations and through exposure to papers like this one on food access we must be aware of the effect of environmental stressors on our patients’ health. Is there more we could learn about those kind of associations? Certainly. This is where a more broadly focused exposome lens could be most effective. 

The authors of the article observed: “The effect of the exposome is not uniform for all individuals but rather intersects across identities precipitating unique outcomes.” The practical reality is that to generate statistically significant data research must look at identities. This doesn’t mean that large population studies are without value. However, it does obligate investigators to include that caveat about the uniqueness of the individual in their conclusions. And, it is our duty as providers to keep this reality in mind as we interpret studies we read in the context of each individual patient. 

When it comes to healthcare delivery at the structural level, I am concerned that we are moving in a direction that is making it more difficult for the provider to become familiar with the patient’s exposome. I am talking about an over-reliance on the team care delivery model that too often results in the “We never/seldom see the same provider” patient complaint.

I don’t care how slick and user-friendly a practice’s EHR system is; the best way to learn about a patient’s exposome is by repeated exposure (pun unintended) to the same provider. This isn’t always possible, and a well-crafted and conscientiously managed EHR can fill in some of the gaps. But, it is a distant second best. 

Awareness of the importance of the exposome is only the starting point. Finding the political will to make the changes necessary to improve our patients’ outcomes is the bigger challenge. Grocery stores well-stocked with healthy foods don’t just pop up where we want them because we think they may hold answer to preventing pediatric obesity.

 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

If we’ve learned anything about obesity prevention it’s that if we wait too long the die is cast and our success rate is nil. The GLP-1 antagonists seem to be a workable solution for treating the adult and adolescent population, but I have been afraid that their success will divert too much of our attention away from prevention.

Fortunately, there still seems to be a few researchers committed to the age group in which obesity could be headed off before our only option is treatment. In one recent study, “Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity,” researchers collected data from more than 28,000 children in 55 cohorts during the period from 1994 to 2023). The investigators found that residence in a low–food access, low-income neighborhoods during pregnancy and early childhood was associated with higher BMI “Z” scores, a higher risk of obesity, and severe obesity in childhood. The researchers defined low food access as living greater than 0.5 miles away from a grocery store in an urban setting or greater than 10 minutes away in a rural setting. I don’t think those associations should surprise us, but having some data from a large population may be valuable should we ever find the political will to undertake any steps toward prevention.

I found a Viewpoint article published 2 weeks earlier in the same journal, titled, “The Exposome as a Key to Understanding Pediatric Health Disparities.” I know what the “biome” is and have heard gastroenterologists expound on the power that billions of our little single-celled friends residing in our gut have on seemingly unrelated and spatially distant events in our body. But, “exposome” was a new word for me, although it turns out the concept is simple and one I had harbored since late childhood. 

 

The opening sentence of the article reads “One’s environment profoundly changes health outcomes throughout one’s lifespan.” That truism was obvious to my 7-year-old self as I observed my playmates who lived in a poorly kept house in the less desirable area two blocks away and didn’t eat breakfast and were sick more often than the rest of us more-fortunates.

The authors define the exposome as the “totality of an individual’s non-genetic exposures, including psychosocial experiences, structural social determinants, chemical pollution, and neighborhood infrastructure.” This seems to be a pretty complete description of the nurture side of the nature versus nurture conversation. 

I suspect that, like me, most of you through observation and intuition have included your own interpretation of the exposome in your professional activities. However, the authors feel we could be more robust in our efforts and claim that “current pediatric practice largely neglects to characterize health disparities in terms of salient environmental practices.” They go on to call for incorporation of an “exposome lens in pediatric research and healthcare delivery.”

I’m not sure this is a valid criticism. There is certainly more that could be done when it comes to research that examines the effect of environmental stressors. And, I suspect the authors would view this recent paper on the association between neighborhood food access as a step in the right direction. However, when it comes to healthcare delivery, at least at the level where the stethoscope meets the chest, I think, or at least hope, the authors are underestimating the observational skills and sensitivity of primary care providers.

We were all taught to take an appropriate medical history when evaluating a patient. And, through our formal education, our personal observations and through exposure to papers like this one on food access we must be aware of the effect of environmental stressors on our patients’ health. Is there more we could learn about those kind of associations? Certainly. This is where a more broadly focused exposome lens could be most effective. 

The authors of the article observed: “The effect of the exposome is not uniform for all individuals but rather intersects across identities precipitating unique outcomes.” The practical reality is that to generate statistically significant data research must look at identities. This doesn’t mean that large population studies are without value. However, it does obligate investigators to include that caveat about the uniqueness of the individual in their conclusions. And, it is our duty as providers to keep this reality in mind as we interpret studies we read in the context of each individual patient. 

When it comes to healthcare delivery at the structural level, I am concerned that we are moving in a direction that is making it more difficult for the provider to become familiar with the patient’s exposome. I am talking about an over-reliance on the team care delivery model that too often results in the “We never/seldom see the same provider” patient complaint.

I don’t care how slick and user-friendly a practice’s EHR system is; the best way to learn about a patient’s exposome is by repeated exposure (pun unintended) to the same provider. This isn’t always possible, and a well-crafted and conscientiously managed EHR can fill in some of the gaps. But, it is a distant second best. 

Awareness of the importance of the exposome is only the starting point. Finding the political will to make the changes necessary to improve our patients’ outcomes is the bigger challenge. Grocery stores well-stocked with healthy foods don’t just pop up where we want them because we think they may hold answer to preventing pediatric obesity.

 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

If we’ve learned anything about obesity prevention it’s that if we wait too long the die is cast and our success rate is nil. The GLP-1 antagonists seem to be a workable solution for treating the adult and adolescent population, but I have been afraid that their success will divert too much of our attention away from prevention.

Fortunately, there still seems to be a few researchers committed to the age group in which obesity could be headed off before our only option is treatment. In one recent study, “Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity,” researchers collected data from more than 28,000 children in 55 cohorts during the period from 1994 to 2023). The investigators found that residence in a low–food access, low-income neighborhoods during pregnancy and early childhood was associated with higher BMI “Z” scores, a higher risk of obesity, and severe obesity in childhood. The researchers defined low food access as living greater than 0.5 miles away from a grocery store in an urban setting or greater than 10 minutes away in a rural setting. I don’t think those associations should surprise us, but having some data from a large population may be valuable should we ever find the political will to undertake any steps toward prevention.

I found a Viewpoint article published 2 weeks earlier in the same journal, titled, “The Exposome as a Key to Understanding Pediatric Health Disparities.” I know what the “biome” is and have heard gastroenterologists expound on the power that billions of our little single-celled friends residing in our gut have on seemingly unrelated and spatially distant events in our body. But, “exposome” was a new word for me, although it turns out the concept is simple and one I had harbored since late childhood. 

 

The opening sentence of the article reads “One’s environment profoundly changes health outcomes throughout one’s lifespan.” That truism was obvious to my 7-year-old self as I observed my playmates who lived in a poorly kept house in the less desirable area two blocks away and didn’t eat breakfast and were sick more often than the rest of us more-fortunates.

The authors define the exposome as the “totality of an individual’s non-genetic exposures, including psychosocial experiences, structural social determinants, chemical pollution, and neighborhood infrastructure.” This seems to be a pretty complete description of the nurture side of the nature versus nurture conversation. 

I suspect that, like me, most of you through observation and intuition have included your own interpretation of the exposome in your professional activities. However, the authors feel we could be more robust in our efforts and claim that “current pediatric practice largely neglects to characterize health disparities in terms of salient environmental practices.” They go on to call for incorporation of an “exposome lens in pediatric research and healthcare delivery.”

I’m not sure this is a valid criticism. There is certainly more that could be done when it comes to research that examines the effect of environmental stressors. And, I suspect the authors would view this recent paper on the association between neighborhood food access as a step in the right direction. However, when it comes to healthcare delivery, at least at the level where the stethoscope meets the chest, I think, or at least hope, the authors are underestimating the observational skills and sensitivity of primary care providers.

We were all taught to take an appropriate medical history when evaluating a patient. And, through our formal education, our personal observations and through exposure to papers like this one on food access we must be aware of the effect of environmental stressors on our patients’ health. Is there more we could learn about those kind of associations? Certainly. This is where a more broadly focused exposome lens could be most effective. 

The authors of the article observed: “The effect of the exposome is not uniform for all individuals but rather intersects across identities precipitating unique outcomes.” The practical reality is that to generate statistically significant data research must look at identities. This doesn’t mean that large population studies are without value. However, it does obligate investigators to include that caveat about the uniqueness of the individual in their conclusions. And, it is our duty as providers to keep this reality in mind as we interpret studies we read in the context of each individual patient. 

When it comes to healthcare delivery at the structural level, I am concerned that we are moving in a direction that is making it more difficult for the provider to become familiar with the patient’s exposome. I am talking about an over-reliance on the team care delivery model that too often results in the “We never/seldom see the same provider” patient complaint.

I don’t care how slick and user-friendly a practice’s EHR system is; the best way to learn about a patient’s exposome is by repeated exposure (pun unintended) to the same provider. This isn’t always possible, and a well-crafted and conscientiously managed EHR can fill in some of the gaps. But, it is a distant second best. 

Awareness of the importance of the exposome is only the starting point. Finding the political will to make the changes necessary to improve our patients’ outcomes is the bigger challenge. Grocery stores well-stocked with healthy foods don’t just pop up where we want them because we think they may hold answer to preventing pediatric obesity.

 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

TOPLINE:

US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.

METHODOLOGY:

• Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
• Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
• International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.

TAKEAWAY:

• Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
• Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
• American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
• The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.

IN PRACTICE:

“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.

SOURCE:

The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.

LIMITATIONS:

According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.

DISCLOSURES:

The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.

METHODOLOGY:

• Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
• Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
• International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.

TAKEAWAY:

• Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
• Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
• American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
• The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.

IN PRACTICE:

“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.

SOURCE:

The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.

LIMITATIONS:

According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.

DISCLOSURES:

The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.

METHODOLOGY:

• Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
• Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
• International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.

TAKEAWAY:

• Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
• Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
• American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
• The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.

IN PRACTICE:

“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.

SOURCE:

The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.

LIMITATIONS:

According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.

DISCLOSURES:

The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.

But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).

“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

“But that’s not really happening now,” she added.

Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.

Here’s what the latest research shows about GLP-1s’ side effects.

 

Most Common: Gastrointestinal Issues

Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.

• In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
• Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.

Apovian finds that careful dosage helps her patients avoid the worst effects.

“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”

If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.

Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.

 

Questions About Causation: Depression and Suicidality

About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.

Further research has been more reassuring:

• Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
• A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
• Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.

There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.

“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”

In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.

This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.

 

Possible Link: Ocular Symptoms

Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:

• One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
• This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
• But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.

One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.

 

Possible Trouble: Pulmonary Aspiration Under Sedation

Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.

GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:

• Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
• Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
• Assessment on the day of the procedure for possible delayed gastric emptying.
• Preoperative dietary modifications, which might include switching to a liquid diet.

Rare: Serious Effects

And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:

• Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
• Colonic ischemia in association with tirzepatide.
• Acute pancreatitis leading to death in association with semaglutide.
• Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.

Benefits Outweigh Risks

When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.

Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.

“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”

And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.

 

A version of this article first appeared on Medscape.com.

Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.

But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).

“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

“But that’s not really happening now,” she added.

Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.

Here’s what the latest research shows about GLP-1s’ side effects.

 

Most Common: Gastrointestinal Issues

Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.

• In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
• Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.

Apovian finds that careful dosage helps her patients avoid the worst effects.

“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”

If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.

Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.

 

Questions About Causation: Depression and Suicidality

About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.

Further research has been more reassuring:

• Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
• A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
• Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.

There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.

“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”

In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.

This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.

 

Possible Link: Ocular Symptoms

Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:

• One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
• This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
• But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.

One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.

 

Possible Trouble: Pulmonary Aspiration Under Sedation

Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.

GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:

• Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
• Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
• Assessment on the day of the procedure for possible delayed gastric emptying.
• Preoperative dietary modifications, which might include switching to a liquid diet.

Rare: Serious Effects

And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:

• Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
• Colonic ischemia in association with tirzepatide.
• Acute pancreatitis leading to death in association with semaglutide.
• Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.

Benefits Outweigh Risks

When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.

Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.

“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”

And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.

 

A version of this article first appeared on Medscape.com.

Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.

But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).

“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

“But that’s not really happening now,” she added.

Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.

Here’s what the latest research shows about GLP-1s’ side effects.

 

Most Common: Gastrointestinal Issues

Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.

• In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
• Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.

Apovian finds that careful dosage helps her patients avoid the worst effects.

“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”

If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.

Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.

 

Questions About Causation: Depression and Suicidality

About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.

Further research has been more reassuring:

• Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
• A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
• Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.

There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.

“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”

In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.

This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.

 

Possible Link: Ocular Symptoms

Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:

• One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
• This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
• But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.

One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.

 

Possible Trouble: Pulmonary Aspiration Under Sedation

Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.

GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:

• Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
• Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
• Assessment on the day of the procedure for possible delayed gastric emptying.
• Preoperative dietary modifications, which might include switching to a liquid diet.

Rare: Serious Effects

And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:

• Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
• Colonic ischemia in association with tirzepatide.
• Acute pancreatitis leading to death in association with semaglutide.
• Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.

Benefits Outweigh Risks

When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.

Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.

“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”

And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.

 

A version of this article first appeared on Medscape.com.

Rates of overweight and obesity have more than doubled in the United States during the last three decades, according to a new analysis. By 2050, it’s anticipated that 213 million adults (age, > 25 years) and 43 million children and adolescents will have overweight or obesity. The results led authors of a study to describe obesity as having reached a “crisis point” requiring urgent action and interventions.

Are glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed and prescribed for diabetes and now approved for weight loss, the answer? 

Their popularity is certainly surging. Between the last 6 months of 2022 vs the last 6 months of 2024, the number of patients prescribed GLP-1 RAs increased by 132.6%. This is also reflected in a shift in public awareness, with a recent survey of US adults finding that 32% of respondents had heard “a lot” about these drugs, up from 19% in 2023.

GLP-1 RAs (including tirzepatide, which targets not only the GLP-1 receptor but also the glucose-dependent insulinotropic polypeptide receptor) have shown efficacy in weight loss. A 2022 review and meta-analysis of 22 trials (17,183 patients) found that 50.2% and 17.5% of those treated with GLP-1 RAs had a ≥ 5% and ≥ 10% weight loss, respectively, compared with placebo. A 2023 review of 41 trials (15,135 patients) found that compared with controls, GLP-1 RAs significantly reduced body weight, body mass index, waist circumference, and waist-to-hip ratio.

“GLP-1 RAs are great medications,” Andres Acosta, MD, PhD, director of the Precision Medicine for Obesity Laboratory, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. “We’ve been using them for almost two decades. But now there’s excitement about their utility in treating obesity.”

 

Treating the Four Categories of Obesity 

Daniel Drucker, MD, senior investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, is a pioneer in diabetes treatment and particularly in the development of GLP-1 RAs. Drucker told Medscape Medical News that despite the efficacy and enormous potential of GLP-1 RAs, “we know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them.”

The number of individuals who don’t respond to or aren’t able to tolerate GLP-1 RAs “might be small — less than 10% of people who try to take them — but we don’t fully understand the differences in response across different individuals,” Drucker said.

Acosta agreed, adding that it’s “essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.”

Acosta’s group has spent more than a decade engaged in efforts to identify unique characteristics among patients with obesity and has succeeded in identifying four obesity phenotypes.

“What matters in the space of GLP-1 is that using this classification, we can identify the best responders and those who don’t respond.” 

The first phenotype, described as “Hungry Gut” (HG), includes patients with abnormal postprandial satiety. “Although they may be satiated at the end of a meal, they have accelerated gastric emptying and therefore feel hungry between meals and want to keep eating,” he said.

There are also patients who experience abnormal satiety during meals. According to Acosta, these are the patients who will return to the table for second and third helpings. “They don’t feel full and continue to eat more and more in a single sitting” — a phenomenon referred to as “Hungry Brain.”

The third phenotype — “Emotional Hunger” — consists of people who are “hedonic” about food or engage in emotional eating behavior, whereas in the fourth group, people have “an abnormal metabolism in which they don’t burn enough calories. They have an inefficient metabolic rate.” This latter phenomenon is called “Slow Burn.”

Acosta and colleagues randomized 312 patients attending a weight management center to phenotype-guided or non–phenotype-guided treatment with anti-obesity medications (phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide). The phenotype-guided approach was associated with a 1.75-fold greater weight loss after 1 year than the non–phenotype-guided approach (mean weight loss, 15.9% vs 9.0%, respectively).

 

GLP-1 RAs: Not One-Size-Fits-All

Acosta’s group has developed a genetic test that uses patients’ saliva to identify their obesity phenotype, with the aim of predicting the best responders to GLP-1 RAs. The test, MyPhenome genetic obesity test, is licensed by Acosta’s lab and available through Phenomix Sciences.

Acosta and colleagues presented their findings at the American Gastroenterological Association’s 2024 annual meeting regarding a machine-learning gene risk score (ML-GRS) they developed to predict HG, based on saliva and blood samples. Their genetic studies generated a ML-GRS that classified participants with obesity along a continuum from “HG Positive” (HG+) to “HG Negative” (HG−). Compared with the HG− participants, those who were HG+ had superior total body weight loss with semaglutide at 9 and 12 months. When used to predict response, the ML-GRS had an area under the curve of 0.76 (P = .04) and a positive predictive value of 0.95.

According to Acosta, HG+ patients are “the best responders to the GLP-1 RAs, although we don’t yet understand the mechanism of why they have the phenomenon of abnormal postprandial satiety. It may be an abnormal genetic pathway or abnormal secretion of GLP-1. More studies are needed.”

He noted that GLP-1 RAs “might also be helpful with the second [Hungry Brain] category, but these patients do better with phentermine-topiramate,” as demonstrated in a 2023 study conducted by Acosta and colleagues.

His group has also studied which lifestyle interventions are most effective for each phenotype. “When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement,” he reported.

“Treating obesity no longer needs to be trial-and-error, but should be done using precision medicine because one size doesn’t fit all,” Acosta said.

 

Concerning Side Effects

The popular media has featured stories about individuals who took GLP-1 RAs for weight loss and experienced serious side effects, including a recent account of a British nurse who died after taking tirzepatide. As reported by the BBC, the nurse’s death certificate listed multiple organ failure, septic shock, and pancreatitis as the immediate causes of death, with the “use of prescribed tirzepatide” recorded as a contributing factor. The report went on to note that there were 23 suspected deaths in the United Kingdom tied to semaglutide since 2019.

Beyond brand-name products, there are also risks associated with GLP-1 RAs manufactured by compounding pharmacies. In early November, CNN reported that compounded semaglutide has been linked to at least 10 deaths. Because of a prior shortage of tirzepatide, the US Food and Drug Administration (FDA) had allowed compounding pharmacies to manufacture the drug. In October, the FDA clarified that it won’t take legal action against compounders, even now that the shortage has been resolved.

A pharmacovigilance study using the FDA Adverse Event Reporting System identified “potential safety signals of increased mortality and serious adverse event reporting” associated with certain GLP-1 RAs — especially in younger patients and women (P < .0001 for both groups).

The most common side effects reported with GLP-1 RAs are gastrointestinal events, such as nausea, diarrhea, constipation, and vomiting. Most occur during dose initiation and escalation and wane over the following weeks. However, studies have also reported severe side effects, including a higher risk for pancreatitis, bowel obstruction, and gastroparesis, as well as a significantly higher risk for gallbladder and biliary diseases. In fact, according to one study, patients with diabetes taking GLP-1 RAs reported gastrointestinal-related issues as a “prominent factor” in their decision to discontinue taking these medications.

Several types of cancer are potentially associated with GLP-1 RAs, but findings regarding this potential link have been inconsistent. In a recent review article, Drucker noted there were only inconsistent data linking GLP-1 RAs with thyroid cancer and medullary thyroid cancer and that their potential association with pancreatic has “not been supported by results from randomized controlled trials or real-world data.” 

Concerns have been raised about loss of lean mass and muscle strength and function, especially in older individuals with obesity and advanced liver, cardiovascular, or kidney disease. However, as Drucker pointed out in his review article, muscle function may not correlate with the loss of lean mass. In fact, there are “consistent reductions” in lean mass after bariatric surgery, but “little evidence to date for impairment of muscle function.” He added that newer GLP-1 agents under development for obesity treatment are focusing on “developing complementary therapies that preferentially reduce adipose tissue, while sparing lean mass.”

As covered by Medscape Medical News, there have been reports of potential suicidal ideation associated with GLP-1 RAs. This triggered a 2023 review from the European Medicines Agency. However, recent results from a cohort study and a post hoc analysis of randomized controlled trials concluded that there is no evidence that these drugs increase suicidal ideation or behavior.

In early November, the FDA updated the labels for the GLP-1 RAs to include a warning regarding pulmonary aspiration during general anesthesia or deep sedation. Guidance from a group of societies, led by the American Society of Anesthesiologists, contains recommendations regarding nuances of addressing this concern in surgical patients taking these agents.

 

Not a Standalone Treatment

Marc-Andre Cornier, MD, professor of medicine, James A. Keating Endowed Chair in Diabetes, and director of the Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News that GLP-1 RAs should not be viewed as cosmetic interventions but rather as medical treatments, “not only for weight loss but to reverse obesity-associated complications.” 

Moreover, they should be used “as an adjunct to lifestyle changes,” emphasized Cornier. “We want our patients to have a high-quality diet with high protein content, fluid, vitamins, and minerals, and we want them to exercise.” Especially with the concern of potential loss of muscle mass with these agents, “resistance exercise might help mitigate that concern.”

Recently published recommendations can assist clinicians in guiding patients taking GLP-1 RAs to optimize nutrition. The recommendations note that patients should be referred to a registered dietitian to “complement and support” treatment with anti-obesity medications.

 

What Do Patients Want?

Despite the ever-rising popularity of GLP-1 RAs, a new national survey of over 2200 US adults conducted by the Physicians Committee for Responsible Medicine suggests that most Americans don’t want to use them. Among those who wanted to lose weight, almost three-quarters “disagreed” or “strongly disagreed” with the idea of taking a weight-loss injectable, and 68% of those who wanted to lose weight “agreed” or “strongly agreed” that they would be willing to try a plant-based diet, if it could lead to significant weight loss.

Moreover, many individuals treated with GLP-1 RAs discontinue their use, despite the probability of regaining the weight, according to a report that found only 46.3% of GLP-1 users were still taking the medications at 6 months and only 32.3% at 1 year. The authors commented that their real-world findings show a “substantially lower” 1-year persistence rate, compared with the rate reported in clinical trials. They suggest that the financial burden (> $12,000/year) may contribute to discontinuation.

Discontinuation of GLP-1 RAs can lead to worsening cardiometabolic parameters, with a potential increased risk for adverse outcomes; moreover, weight cycling (“yo-yo dieting”) carries its own risks. In light of these concerns, it’s particularly important to select appropriate patients and to determine whether potential short-term therapy has any enduring benefit.

Acosta agreed. “It’s exciting when looking at the data on how to find the best responders and who should make the effort to take these medications — not only in terms of side effects but also in terms of cost and which patients will receive maximum benefits and should be covered by insurance.” 

Drucker has served as a consultant or speaker for Altimmune, Amgen, AstraZeneca, Arrowhead, Boehringer Ingelheim, Kallyope, Merck Research Laboratories, Novo Nordisk, Pfizer, and Zealand Pharma. He holds nonexercised options in Kallyope. Mount Sinai Hospital receives research support for investigator-initiated studies in the Drucker laboratory from Amgen, Novo Nordisk, Pfizer, and Zealand Pharma. Gila Therapeutics and Phenomix Sciences have licensed Acosta’s research technologies from University of Florida and Mayo Clinic. Acosta received consultant fees in the last 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, Currax, Nestlé, Phenomix Sciences, Bausch Health, and Rare Disease. He received funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, Rhythm Pharmaceuticals, Regeneron Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk. In the past, Cornier has served as a consultant for Novo Nordisk.

 

A version of this article first appeared on Medscape.com.

Rates of overweight and obesity have more than doubled in the United States during the last three decades, according to a new analysis. By 2050, it’s anticipated that 213 million adults (age, > 25 years) and 43 million children and adolescents will have overweight or obesity. The results led authors of a study to describe obesity as having reached a “crisis point” requiring urgent action and interventions.

Are glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed and prescribed for diabetes and now approved for weight loss, the answer? 

Their popularity is certainly surging. Between the last 6 months of 2022 vs the last 6 months of 2024, the number of patients prescribed GLP-1 RAs increased by 132.6%. This is also reflected in a shift in public awareness, with a recent survey of US adults finding that 32% of respondents had heard “a lot” about these drugs, up from 19% in 2023.

GLP-1 RAs (including tirzepatide, which targets not only the GLP-1 receptor but also the glucose-dependent insulinotropic polypeptide receptor) have shown efficacy in weight loss. A 2022 review and meta-analysis of 22 trials (17,183 patients) found that 50.2% and 17.5% of those treated with GLP-1 RAs had a ≥ 5% and ≥ 10% weight loss, respectively, compared with placebo. A 2023 review of 41 trials (15,135 patients) found that compared with controls, GLP-1 RAs significantly reduced body weight, body mass index, waist circumference, and waist-to-hip ratio.

“GLP-1 RAs are great medications,” Andres Acosta, MD, PhD, director of the Precision Medicine for Obesity Laboratory, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. “We’ve been using them for almost two decades. But now there’s excitement about their utility in treating obesity.”

 

Treating the Four Categories of Obesity 

Daniel Drucker, MD, senior investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, is a pioneer in diabetes treatment and particularly in the development of GLP-1 RAs. Drucker told Medscape Medical News that despite the efficacy and enormous potential of GLP-1 RAs, “we know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them.”

The number of individuals who don’t respond to or aren’t able to tolerate GLP-1 RAs “might be small — less than 10% of people who try to take them — but we don’t fully understand the differences in response across different individuals,” Drucker said.

Acosta agreed, adding that it’s “essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.”

Acosta’s group has spent more than a decade engaged in efforts to identify unique characteristics among patients with obesity and has succeeded in identifying four obesity phenotypes.

“What matters in the space of GLP-1 is that using this classification, we can identify the best responders and those who don’t respond.” 

The first phenotype, described as “Hungry Gut” (HG), includes patients with abnormal postprandial satiety. “Although they may be satiated at the end of a meal, they have accelerated gastric emptying and therefore feel hungry between meals and want to keep eating,” he said.

There are also patients who experience abnormal satiety during meals. According to Acosta, these are the patients who will return to the table for second and third helpings. “They don’t feel full and continue to eat more and more in a single sitting” — a phenomenon referred to as “Hungry Brain.”

The third phenotype — “Emotional Hunger” — consists of people who are “hedonic” about food or engage in emotional eating behavior, whereas in the fourth group, people have “an abnormal metabolism in which they don’t burn enough calories. They have an inefficient metabolic rate.” This latter phenomenon is called “Slow Burn.”

Acosta and colleagues randomized 312 patients attending a weight management center to phenotype-guided or non–phenotype-guided treatment with anti-obesity medications (phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide). The phenotype-guided approach was associated with a 1.75-fold greater weight loss after 1 year than the non–phenotype-guided approach (mean weight loss, 15.9% vs 9.0%, respectively).

 

GLP-1 RAs: Not One-Size-Fits-All

Acosta’s group has developed a genetic test that uses patients’ saliva to identify their obesity phenotype, with the aim of predicting the best responders to GLP-1 RAs. The test, MyPhenome genetic obesity test, is licensed by Acosta’s lab and available through Phenomix Sciences.

Acosta and colleagues presented their findings at the American Gastroenterological Association’s 2024 annual meeting regarding a machine-learning gene risk score (ML-GRS) they developed to predict HG, based on saliva and blood samples. Their genetic studies generated a ML-GRS that classified participants with obesity along a continuum from “HG Positive” (HG+) to “HG Negative” (HG−). Compared with the HG− participants, those who were HG+ had superior total body weight loss with semaglutide at 9 and 12 months. When used to predict response, the ML-GRS had an area under the curve of 0.76 (P = .04) and a positive predictive value of 0.95.

According to Acosta, HG+ patients are “the best responders to the GLP-1 RAs, although we don’t yet understand the mechanism of why they have the phenomenon of abnormal postprandial satiety. It may be an abnormal genetic pathway or abnormal secretion of GLP-1. More studies are needed.”

He noted that GLP-1 RAs “might also be helpful with the second [Hungry Brain] category, but these patients do better with phentermine-topiramate,” as demonstrated in a 2023 study conducted by Acosta and colleagues.

His group has also studied which lifestyle interventions are most effective for each phenotype. “When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement,” he reported.

“Treating obesity no longer needs to be trial-and-error, but should be done using precision medicine because one size doesn’t fit all,” Acosta said.

 

Concerning Side Effects

The popular media has featured stories about individuals who took GLP-1 RAs for weight loss and experienced serious side effects, including a recent account of a British nurse who died after taking tirzepatide. As reported by the BBC, the nurse’s death certificate listed multiple organ failure, septic shock, and pancreatitis as the immediate causes of death, with the “use of prescribed tirzepatide” recorded as a contributing factor. The report went on to note that there were 23 suspected deaths in the United Kingdom tied to semaglutide since 2019.

Beyond brand-name products, there are also risks associated with GLP-1 RAs manufactured by compounding pharmacies. In early November, CNN reported that compounded semaglutide has been linked to at least 10 deaths. Because of a prior shortage of tirzepatide, the US Food and Drug Administration (FDA) had allowed compounding pharmacies to manufacture the drug. In October, the FDA clarified that it won’t take legal action against compounders, even now that the shortage has been resolved.

A pharmacovigilance study using the FDA Adverse Event Reporting System identified “potential safety signals of increased mortality and serious adverse event reporting” associated with certain GLP-1 RAs — especially in younger patients and women (P < .0001 for both groups).

The most common side effects reported with GLP-1 RAs are gastrointestinal events, such as nausea, diarrhea, constipation, and vomiting. Most occur during dose initiation and escalation and wane over the following weeks. However, studies have also reported severe side effects, including a higher risk for pancreatitis, bowel obstruction, and gastroparesis, as well as a significantly higher risk for gallbladder and biliary diseases. In fact, according to one study, patients with diabetes taking GLP-1 RAs reported gastrointestinal-related issues as a “prominent factor” in their decision to discontinue taking these medications.

Several types of cancer are potentially associated with GLP-1 RAs, but findings regarding this potential link have been inconsistent. In a recent review article, Drucker noted there were only inconsistent data linking GLP-1 RAs with thyroid cancer and medullary thyroid cancer and that their potential association with pancreatic has “not been supported by results from randomized controlled trials or real-world data.” 

Concerns have been raised about loss of lean mass and muscle strength and function, especially in older individuals with obesity and advanced liver, cardiovascular, or kidney disease. However, as Drucker pointed out in his review article, muscle function may not correlate with the loss of lean mass. In fact, there are “consistent reductions” in lean mass after bariatric surgery, but “little evidence to date for impairment of muscle function.” He added that newer GLP-1 agents under development for obesity treatment are focusing on “developing complementary therapies that preferentially reduce adipose tissue, while sparing lean mass.”

As covered by Medscape Medical News, there have been reports of potential suicidal ideation associated with GLP-1 RAs. This triggered a 2023 review from the European Medicines Agency. However, recent results from a cohort study and a post hoc analysis of randomized controlled trials concluded that there is no evidence that these drugs increase suicidal ideation or behavior.

In early November, the FDA updated the labels for the GLP-1 RAs to include a warning regarding pulmonary aspiration during general anesthesia or deep sedation. Guidance from a group of societies, led by the American Society of Anesthesiologists, contains recommendations regarding nuances of addressing this concern in surgical patients taking these agents.

 

Not a Standalone Treatment

Marc-Andre Cornier, MD, professor of medicine, James A. Keating Endowed Chair in Diabetes, and director of the Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News that GLP-1 RAs should not be viewed as cosmetic interventions but rather as medical treatments, “not only for weight loss but to reverse obesity-associated complications.” 

Moreover, they should be used “as an adjunct to lifestyle changes,” emphasized Cornier. “We want our patients to have a high-quality diet with high protein content, fluid, vitamins, and minerals, and we want them to exercise.” Especially with the concern of potential loss of muscle mass with these agents, “resistance exercise might help mitigate that concern.”

Recently published recommendations can assist clinicians in guiding patients taking GLP-1 RAs to optimize nutrition. The recommendations note that patients should be referred to a registered dietitian to “complement and support” treatment with anti-obesity medications.

 

What Do Patients Want?

Despite the ever-rising popularity of GLP-1 RAs, a new national survey of over 2200 US adults conducted by the Physicians Committee for Responsible Medicine suggests that most Americans don’t want to use them. Among those who wanted to lose weight, almost three-quarters “disagreed” or “strongly disagreed” with the idea of taking a weight-loss injectable, and 68% of those who wanted to lose weight “agreed” or “strongly agreed” that they would be willing to try a plant-based diet, if it could lead to significant weight loss.

Moreover, many individuals treated with GLP-1 RAs discontinue their use, despite the probability of regaining the weight, according to a report that found only 46.3% of GLP-1 users were still taking the medications at 6 months and only 32.3% at 1 year. The authors commented that their real-world findings show a “substantially lower” 1-year persistence rate, compared with the rate reported in clinical trials. They suggest that the financial burden (> $12,000/year) may contribute to discontinuation.

Discontinuation of GLP-1 RAs can lead to worsening cardiometabolic parameters, with a potential increased risk for adverse outcomes; moreover, weight cycling (“yo-yo dieting”) carries its own risks. In light of these concerns, it’s particularly important to select appropriate patients and to determine whether potential short-term therapy has any enduring benefit.

Acosta agreed. “It’s exciting when looking at the data on how to find the best responders and who should make the effort to take these medications — not only in terms of side effects but also in terms of cost and which patients will receive maximum benefits and should be covered by insurance.” 

Drucker has served as a consultant or speaker for Altimmune, Amgen, AstraZeneca, Arrowhead, Boehringer Ingelheim, Kallyope, Merck Research Laboratories, Novo Nordisk, Pfizer, and Zealand Pharma. He holds nonexercised options in Kallyope. Mount Sinai Hospital receives research support for investigator-initiated studies in the Drucker laboratory from Amgen, Novo Nordisk, Pfizer, and Zealand Pharma. Gila Therapeutics and Phenomix Sciences have licensed Acosta’s research technologies from University of Florida and Mayo Clinic. Acosta received consultant fees in the last 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, Currax, Nestlé, Phenomix Sciences, Bausch Health, and Rare Disease. He received funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, Rhythm Pharmaceuticals, Regeneron Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk. In the past, Cornier has served as a consultant for Novo Nordisk.

 

A version of this article first appeared on Medscape.com.

Rates of overweight and obesity have more than doubled in the United States during the last three decades, according to a new analysis. By 2050, it’s anticipated that 213 million adults (age, > 25 years) and 43 million children and adolescents will have overweight or obesity. The results led authors of a study to describe obesity as having reached a “crisis point” requiring urgent action and interventions.

Are glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed and prescribed for diabetes and now approved for weight loss, the answer? 

Their popularity is certainly surging. Between the last 6 months of 2022 vs the last 6 months of 2024, the number of patients prescribed GLP-1 RAs increased by 132.6%. This is also reflected in a shift in public awareness, with a recent survey of US adults finding that 32% of respondents had heard “a lot” about these drugs, up from 19% in 2023.

GLP-1 RAs (including tirzepatide, which targets not only the GLP-1 receptor but also the glucose-dependent insulinotropic polypeptide receptor) have shown efficacy in weight loss. A 2022 review and meta-analysis of 22 trials (17,183 patients) found that 50.2% and 17.5% of those treated with GLP-1 RAs had a ≥ 5% and ≥ 10% weight loss, respectively, compared with placebo. A 2023 review of 41 trials (15,135 patients) found that compared with controls, GLP-1 RAs significantly reduced body weight, body mass index, waist circumference, and waist-to-hip ratio.

“GLP-1 RAs are great medications,” Andres Acosta, MD, PhD, director of the Precision Medicine for Obesity Laboratory, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. “We’ve been using them for almost two decades. But now there’s excitement about their utility in treating obesity.”

 

Treating the Four Categories of Obesity 

Daniel Drucker, MD, senior investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, is a pioneer in diabetes treatment and particularly in the development of GLP-1 RAs. Drucker told Medscape Medical News that despite the efficacy and enormous potential of GLP-1 RAs, “we know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them.”

The number of individuals who don’t respond to or aren’t able to tolerate GLP-1 RAs “might be small — less than 10% of people who try to take them — but we don’t fully understand the differences in response across different individuals,” Drucker said.

Acosta agreed, adding that it’s “essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.”

Acosta’s group has spent more than a decade engaged in efforts to identify unique characteristics among patients with obesity and has succeeded in identifying four obesity phenotypes.

“What matters in the space of GLP-1 is that using this classification, we can identify the best responders and those who don’t respond.” 

The first phenotype, described as “Hungry Gut” (HG), includes patients with abnormal postprandial satiety. “Although they may be satiated at the end of a meal, they have accelerated gastric emptying and therefore feel hungry between meals and want to keep eating,” he said.

There are also patients who experience abnormal satiety during meals. According to Acosta, these are the patients who will return to the table for second and third helpings. “They don’t feel full and continue to eat more and more in a single sitting” — a phenomenon referred to as “Hungry Brain.”

The third phenotype — “Emotional Hunger” — consists of people who are “hedonic” about food or engage in emotional eating behavior, whereas in the fourth group, people have “an abnormal metabolism in which they don’t burn enough calories. They have an inefficient metabolic rate.” This latter phenomenon is called “Slow Burn.”

Acosta and colleagues randomized 312 patients attending a weight management center to phenotype-guided or non–phenotype-guided treatment with anti-obesity medications (phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide). The phenotype-guided approach was associated with a 1.75-fold greater weight loss after 1 year than the non–phenotype-guided approach (mean weight loss, 15.9% vs 9.0%, respectively).

 

GLP-1 RAs: Not One-Size-Fits-All

Acosta’s group has developed a genetic test that uses patients’ saliva to identify their obesity phenotype, with the aim of predicting the best responders to GLP-1 RAs. The test, MyPhenome genetic obesity test, is licensed by Acosta’s lab and available through Phenomix Sciences.

Acosta and colleagues presented their findings at the American Gastroenterological Association’s 2024 annual meeting regarding a machine-learning gene risk score (ML-GRS) they developed to predict HG, based on saliva and blood samples. Their genetic studies generated a ML-GRS that classified participants with obesity along a continuum from “HG Positive” (HG+) to “HG Negative” (HG−). Compared with the HG− participants, those who were HG+ had superior total body weight loss with semaglutide at 9 and 12 months. When used to predict response, the ML-GRS had an area under the curve of 0.76 (P = .04) and a positive predictive value of 0.95.

According to Acosta, HG+ patients are “the best responders to the GLP-1 RAs, although we don’t yet understand the mechanism of why they have the phenomenon of abnormal postprandial satiety. It may be an abnormal genetic pathway or abnormal secretion of GLP-1. More studies are needed.”

He noted that GLP-1 RAs “might also be helpful with the second [Hungry Brain] category, but these patients do better with phentermine-topiramate,” as demonstrated in a 2023 study conducted by Acosta and colleagues.

His group has also studied which lifestyle interventions are most effective for each phenotype. “When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement,” he reported.

“Treating obesity no longer needs to be trial-and-error, but should be done using precision medicine because one size doesn’t fit all,” Acosta said.

 

Concerning Side Effects

The popular media has featured stories about individuals who took GLP-1 RAs for weight loss and experienced serious side effects, including a recent account of a British nurse who died after taking tirzepatide. As reported by the BBC, the nurse’s death certificate listed multiple organ failure, septic shock, and pancreatitis as the immediate causes of death, with the “use of prescribed tirzepatide” recorded as a contributing factor. The report went on to note that there were 23 suspected deaths in the United Kingdom tied to semaglutide since 2019.

Beyond brand-name products, there are also risks associated with GLP-1 RAs manufactured by compounding pharmacies. In early November, CNN reported that compounded semaglutide has been linked to at least 10 deaths. Because of a prior shortage of tirzepatide, the US Food and Drug Administration (FDA) had allowed compounding pharmacies to manufacture the drug. In October, the FDA clarified that it won’t take legal action against compounders, even now that the shortage has been resolved.

A pharmacovigilance study using the FDA Adverse Event Reporting System identified “potential safety signals of increased mortality and serious adverse event reporting” associated with certain GLP-1 RAs — especially in younger patients and women (P < .0001 for both groups).

The most common side effects reported with GLP-1 RAs are gastrointestinal events, such as nausea, diarrhea, constipation, and vomiting. Most occur during dose initiation and escalation and wane over the following weeks. However, studies have also reported severe side effects, including a higher risk for pancreatitis, bowel obstruction, and gastroparesis, as well as a significantly higher risk for gallbladder and biliary diseases. In fact, according to one study, patients with diabetes taking GLP-1 RAs reported gastrointestinal-related issues as a “prominent factor” in their decision to discontinue taking these medications.

Several types of cancer are potentially associated with GLP-1 RAs, but findings regarding this potential link have been inconsistent. In a recent review article, Drucker noted there were only inconsistent data linking GLP-1 RAs with thyroid cancer and medullary thyroid cancer and that their potential association with pancreatic has “not been supported by results from randomized controlled trials or real-world data.” 

Concerns have been raised about loss of lean mass and muscle strength and function, especially in older individuals with obesity and advanced liver, cardiovascular, or kidney disease. However, as Drucker pointed out in his review article, muscle function may not correlate with the loss of lean mass. In fact, there are “consistent reductions” in lean mass after bariatric surgery, but “little evidence to date for impairment of muscle function.” He added that newer GLP-1 agents under development for obesity treatment are focusing on “developing complementary therapies that preferentially reduce adipose tissue, while sparing lean mass.”

As covered by Medscape Medical News, there have been reports of potential suicidal ideation associated with GLP-1 RAs. This triggered a 2023 review from the European Medicines Agency. However, recent results from a cohort study and a post hoc analysis of randomized controlled trials concluded that there is no evidence that these drugs increase suicidal ideation or behavior.

In early November, the FDA updated the labels for the GLP-1 RAs to include a warning regarding pulmonary aspiration during general anesthesia or deep sedation. Guidance from a group of societies, led by the American Society of Anesthesiologists, contains recommendations regarding nuances of addressing this concern in surgical patients taking these agents.

 

Not a Standalone Treatment

Marc-Andre Cornier, MD, professor of medicine, James A. Keating Endowed Chair in Diabetes, and director of the Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News that GLP-1 RAs should not be viewed as cosmetic interventions but rather as medical treatments, “not only for weight loss but to reverse obesity-associated complications.” 

Moreover, they should be used “as an adjunct to lifestyle changes,” emphasized Cornier. “We want our patients to have a high-quality diet with high protein content, fluid, vitamins, and minerals, and we want them to exercise.” Especially with the concern of potential loss of muscle mass with these agents, “resistance exercise might help mitigate that concern.”

Recently published recommendations can assist clinicians in guiding patients taking GLP-1 RAs to optimize nutrition. The recommendations note that patients should be referred to a registered dietitian to “complement and support” treatment with anti-obesity medications.

 

What Do Patients Want?

Despite the ever-rising popularity of GLP-1 RAs, a new national survey of over 2200 US adults conducted by the Physicians Committee for Responsible Medicine suggests that most Americans don’t want to use them. Among those who wanted to lose weight, almost three-quarters “disagreed” or “strongly disagreed” with the idea of taking a weight-loss injectable, and 68% of those who wanted to lose weight “agreed” or “strongly agreed” that they would be willing to try a plant-based diet, if it could lead to significant weight loss.

Moreover, many individuals treated with GLP-1 RAs discontinue their use, despite the probability of regaining the weight, according to a report that found only 46.3% of GLP-1 users were still taking the medications at 6 months and only 32.3% at 1 year. The authors commented that their real-world findings show a “substantially lower” 1-year persistence rate, compared with the rate reported in clinical trials. They suggest that the financial burden (> $12,000/year) may contribute to discontinuation.

Discontinuation of GLP-1 RAs can lead to worsening cardiometabolic parameters, with a potential increased risk for adverse outcomes; moreover, weight cycling (“yo-yo dieting”) carries its own risks. In light of these concerns, it’s particularly important to select appropriate patients and to determine whether potential short-term therapy has any enduring benefit.

Acosta agreed. “It’s exciting when looking at the data on how to find the best responders and who should make the effort to take these medications — not only in terms of side effects but also in terms of cost and which patients will receive maximum benefits and should be covered by insurance.” 

Drucker has served as a consultant or speaker for Altimmune, Amgen, AstraZeneca, Arrowhead, Boehringer Ingelheim, Kallyope, Merck Research Laboratories, Novo Nordisk, Pfizer, and Zealand Pharma. He holds nonexercised options in Kallyope. Mount Sinai Hospital receives research support for investigator-initiated studies in the Drucker laboratory from Amgen, Novo Nordisk, Pfizer, and Zealand Pharma. Gila Therapeutics and Phenomix Sciences have licensed Acosta’s research technologies from University of Florida and Mayo Clinic. Acosta received consultant fees in the last 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, Currax, Nestlé, Phenomix Sciences, Bausch Health, and Rare Disease. He received funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, Rhythm Pharmaceuticals, Regeneron Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk. In the past, Cornier has served as a consultant for Novo Nordisk.

 

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Recently, there have been two somewhat conflicting recommendations about how to deal with our patients who are on incretin hormone therapy before undergoing elective surgical procedures. 

First, the FDA [Food and Drug Administration] has updated the package inserts for all of these incretins, meaning the glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic (GIP)/GLP-1 receptor agonist tirzepatide, with a warning about pulmonary aspiration during general anesthesia or deep sedation. They instruct patients to let healthcare providers know of any planned surgeries or procedures. This has come about because of postmarketing experience in which patients who are on GLP-1 receptor agonists have had residual gastric contents found despite reported adherence to preoperative fasting recommendations.

The problem with this is that the FDA says they don’t really actually know what to tell us to do or not to do because we don’t have knowledge as to how to truly mitigate the risk for pulmonary aspiration during general anesthesia or deep sedation. They don’t know if modifying preoperative fasting recommendations should be changed or if temporary discontinuation of the drugs could reduce this problem. They really don’t know what to tell us to do except to tell us that this is a problem we should discuss with our patients. 

At about the same time, a society guideline— and this was from a number of different societies, including the American Society of Anesthesiologists — stated that most patients should continue taking their GLP-1 receptor agonist before elective surgery.

This struck me as somewhat discordant from what the FDA said, although the FDA also says they don’t know quite what to tell us to do. This clinical guideline goes into a bit more detail, and what they think might be a good idea is that patients who are at the highest risk for GI side effects should follow a liquid diet for 24 hours before the procedure.

They basically look at who is at highest risk, and they say the following: Patients in the escalation phase of their incretin therapy — that is, early in treatment when the dose is increasing — are most likely to have delays in gastric emptying because that effect is lessened over time. They say that the elective surgery should be deferred until the escalation phase has passed and the GI symptoms have dissipated.

They’re very clear that patients who have significant GI symptoms, including nausea, vomiting, abdominal pain, constipation, and shortness of breath, should wait until their symptoms have dissipated. 

They think this is something that would be good no matter what dose of drug these patients are on. They do say that you tend to see more issues with gastric emptying in patients at the highest dose of a GLP-1 receptor agonist. They also mention other medical conditions that may slow gastric emptying, such as Parkinson’s disease, which may further modify the perioperative management plan. 

Their proposed solutions that sort of correspond with my proposed solutions include assessing the patient. Obviously, if a patient is going up on the dose of these drugs or having many GI side effects, that’s someone who you probably don’t want to send for elective surgery if you don’t have to. However, if you need to — and possibly in everybody — you might want to withhold the drug for 10-14 days preoperatively to make sure they don’t have significant GI side effects as they’re preparing for their procedure.

One of the things the anesthesiology group was worried about was that glucose levels would go up and patients would have hyperglycemia going into surgery. I’m not so worried about holding a dose or two of one of these agents. I don’t see much hyperglycemia occurring. If it does, you can treat it in other ways. 

If it’s somebody where you think they’re having symptoms but they want to have the procedure anyway, you can put them on a liquid diet for 24 hours or so, so that there’s less of a risk for retained gastric contents, at least solid gastric contents. Anesthesiologists can help with this as well because in many cases, they can do a point-of-care gastric ultrasound to check for retained food or fluid. 

I know this is sort of vague because I don’t have clear recommendations, but I do think it’s important to talk with your patients to assess whether they’re having signs or symptoms of gastroparesis. I think it’s not unreasonable to hold the incretin hormone therapy for one or two doses before a procedure if you have that opportunity, and be sure that the anesthesiologist and surgery team are aware of the fact that the patient has been on one of these agents so that they’re a little more aware of the risk for aspiration.

Anne L. Peters, Professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles, California, has disclosed the following relevant financial relationships: Serve(d) on the advisory board for Abbott Diabetes Care; Becton Dickinson; Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Lexicon Pharmaceuticals, Inc.; Livongo; Medscape; Merck & Co., Inc.; Novo Nordisk; Omada Health; OptumHealth; sanofi; Zafgen Received research support from: Dexcom; MannKind Corporation; Astra Zeneca. Serve(d) as a member of a speakers bureau for: Novo Nordisk.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Recently, there have been two somewhat conflicting recommendations about how to deal with our patients who are on incretin hormone therapy before undergoing elective surgical procedures. 

First, the FDA [Food and Drug Administration] has updated the package inserts for all of these incretins, meaning the glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic (GIP)/GLP-1 receptor agonist tirzepatide, with a warning about pulmonary aspiration during general anesthesia or deep sedation. They instruct patients to let healthcare providers know of any planned surgeries or procedures. This has come about because of postmarketing experience in which patients who are on GLP-1 receptor agonists have had residual gastric contents found despite reported adherence to preoperative fasting recommendations.

The problem with this is that the FDA says they don’t really actually know what to tell us to do or not to do because we don’t have knowledge as to how to truly mitigate the risk for pulmonary aspiration during general anesthesia or deep sedation. They don’t know if modifying preoperative fasting recommendations should be changed or if temporary discontinuation of the drugs could reduce this problem. They really don’t know what to tell us to do except to tell us that this is a problem we should discuss with our patients. 

At about the same time, a society guideline— and this was from a number of different societies, including the American Society of Anesthesiologists — stated that most patients should continue taking their GLP-1 receptor agonist before elective surgery.

This struck me as somewhat discordant from what the FDA said, although the FDA also says they don’t know quite what to tell us to do. This clinical guideline goes into a bit more detail, and what they think might be a good idea is that patients who are at the highest risk for GI side effects should follow a liquid diet for 24 hours before the procedure.

They basically look at who is at highest risk, and they say the following: Patients in the escalation phase of their incretin therapy — that is, early in treatment when the dose is increasing — are most likely to have delays in gastric emptying because that effect is lessened over time. They say that the elective surgery should be deferred until the escalation phase has passed and the GI symptoms have dissipated.

They’re very clear that patients who have significant GI symptoms, including nausea, vomiting, abdominal pain, constipation, and shortness of breath, should wait until their symptoms have dissipated. 

They think this is something that would be good no matter what dose of drug these patients are on. They do say that you tend to see more issues with gastric emptying in patients at the highest dose of a GLP-1 receptor agonist. They also mention other medical conditions that may slow gastric emptying, such as Parkinson’s disease, which may further modify the perioperative management plan. 

Their proposed solutions that sort of correspond with my proposed solutions include assessing the patient. Obviously, if a patient is going up on the dose of these drugs or having many GI side effects, that’s someone who you probably don’t want to send for elective surgery if you don’t have to. However, if you need to — and possibly in everybody — you might want to withhold the drug for 10-14 days preoperatively to make sure they don’t have significant GI side effects as they’re preparing for their procedure.

One of the things the anesthesiology group was worried about was that glucose levels would go up and patients would have hyperglycemia going into surgery. I’m not so worried about holding a dose or two of one of these agents. I don’t see much hyperglycemia occurring. If it does, you can treat it in other ways. 

If it’s somebody where you think they’re having symptoms but they want to have the procedure anyway, you can put them on a liquid diet for 24 hours or so, so that there’s less of a risk for retained gastric contents, at least solid gastric contents. Anesthesiologists can help with this as well because in many cases, they can do a point-of-care gastric ultrasound to check for retained food or fluid. 

I know this is sort of vague because I don’t have clear recommendations, but I do think it’s important to talk with your patients to assess whether they’re having signs or symptoms of gastroparesis. I think it’s not unreasonable to hold the incretin hormone therapy for one or two doses before a procedure if you have that opportunity, and be sure that the anesthesiologist and surgery team are aware of the fact that the patient has been on one of these agents so that they’re a little more aware of the risk for aspiration.

Anne L. Peters, Professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles, California, has disclosed the following relevant financial relationships: Serve(d) on the advisory board for Abbott Diabetes Care; Becton Dickinson; Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Lexicon Pharmaceuticals, Inc.; Livongo; Medscape; Merck & Co., Inc.; Novo Nordisk; Omada Health; OptumHealth; sanofi; Zafgen Received research support from: Dexcom; MannKind Corporation; Astra Zeneca. Serve(d) as a member of a speakers bureau for: Novo Nordisk.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Recently, there have been two somewhat conflicting recommendations about how to deal with our patients who are on incretin hormone therapy before undergoing elective surgical procedures. 

First, the FDA [Food and Drug Administration] has updated the package inserts for all of these incretins, meaning the glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic (GIP)/GLP-1 receptor agonist tirzepatide, with a warning about pulmonary aspiration during general anesthesia or deep sedation. They instruct patients to let healthcare providers know of any planned surgeries or procedures. This has come about because of postmarketing experience in which patients who are on GLP-1 receptor agonists have had residual gastric contents found despite reported adherence to preoperative fasting recommendations.

The problem with this is that the FDA says they don’t really actually know what to tell us to do or not to do because we don’t have knowledge as to how to truly mitigate the risk for pulmonary aspiration during general anesthesia or deep sedation. They don’t know if modifying preoperative fasting recommendations should be changed or if temporary discontinuation of the drugs could reduce this problem. They really don’t know what to tell us to do except to tell us that this is a problem we should discuss with our patients. 

At about the same time, a society guideline— and this was from a number of different societies, including the American Society of Anesthesiologists — stated that most patients should continue taking their GLP-1 receptor agonist before elective surgery.

This struck me as somewhat discordant from what the FDA said, although the FDA also says they don’t know quite what to tell us to do. This clinical guideline goes into a bit more detail, and what they think might be a good idea is that patients who are at the highest risk for GI side effects should follow a liquid diet for 24 hours before the procedure.

They basically look at who is at highest risk, and they say the following: Patients in the escalation phase of their incretin therapy — that is, early in treatment when the dose is increasing — are most likely to have delays in gastric emptying because that effect is lessened over time. They say that the elective surgery should be deferred until the escalation phase has passed and the GI symptoms have dissipated.

They’re very clear that patients who have significant GI symptoms, including nausea, vomiting, abdominal pain, constipation, and shortness of breath, should wait until their symptoms have dissipated. 

They think this is something that would be good no matter what dose of drug these patients are on. They do say that you tend to see more issues with gastric emptying in patients at the highest dose of a GLP-1 receptor agonist. They also mention other medical conditions that may slow gastric emptying, such as Parkinson’s disease, which may further modify the perioperative management plan. 

Their proposed solutions that sort of correspond with my proposed solutions include assessing the patient. Obviously, if a patient is going up on the dose of these drugs or having many GI side effects, that’s someone who you probably don’t want to send for elective surgery if you don’t have to. However, if you need to — and possibly in everybody — you might want to withhold the drug for 10-14 days preoperatively to make sure they don’t have significant GI side effects as they’re preparing for their procedure.

One of the things the anesthesiology group was worried about was that glucose levels would go up and patients would have hyperglycemia going into surgery. I’m not so worried about holding a dose or two of one of these agents. I don’t see much hyperglycemia occurring. If it does, you can treat it in other ways. 

If it’s somebody where you think they’re having symptoms but they want to have the procedure anyway, you can put them on a liquid diet for 24 hours or so, so that there’s less of a risk for retained gastric contents, at least solid gastric contents. Anesthesiologists can help with this as well because in many cases, they can do a point-of-care gastric ultrasound to check for retained food or fluid. 

I know this is sort of vague because I don’t have clear recommendations, but I do think it’s important to talk with your patients to assess whether they’re having signs or symptoms of gastroparesis. I think it’s not unreasonable to hold the incretin hormone therapy for one or two doses before a procedure if you have that opportunity, and be sure that the anesthesiologist and surgery team are aware of the fact that the patient has been on one of these agents so that they’re a little more aware of the risk for aspiration.

Anne L. Peters, Professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles, California, has disclosed the following relevant financial relationships: Serve(d) on the advisory board for Abbott Diabetes Care; Becton Dickinson; Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Lexicon Pharmaceuticals, Inc.; Livongo; Medscape; Merck & Co., Inc.; Novo Nordisk; Omada Health; OptumHealth; sanofi; Zafgen Received research support from: Dexcom; MannKind Corporation; Astra Zeneca. Serve(d) as a member of a speakers bureau for: Novo Nordisk.

A version of this article first appeared on Medscape.com.

The principle of parsimony, often referred to as “Occam’s razor,” favors a unifying explanation over multiple ones, as long as both explain the data equally well. This heuristic, widely used in medical practice, advocates for simpler explanations rather than complex theories. However, its application in modern medicine has sparked debate.

“Hickam’s dictum,” a counterargument to Occam’s razor, asserts that patients — especially as populations grow older and more fragile — can simultaneously have multiple, unrelated diagnoses. These contrasting perspectives on clinical reasoning, balancing diagnostic simplicity and complexity, are both used in daily medical practice.

But are these two axioms truly in conflict, or is this a false dichotomy?

 

Occam’s Razor and Simple Diagnoses

Interpersonal variability in diagnostic approaches, shaped by the subjective nature of many judgments, complicates the formal evaluation of diagnostic parsimony (Occam’s razor). Indirect evidence suggests that prioritizing simplicity in diagnosis can result in under-detection of secondary conditions, particularly in patients with chronic illnesses.

For example, older patients with a known chronic illness were found to have a 30%-60% lower likelihood of being treated for an unrelated secondary diagnosis than matched peers without the chronic condition. Other studies indicate that a readily available, simple diagnosis can lead clinicians to prematurely close their diagnostic reasoning, overlooking other significant illnesses.

 

Beyond Hickam’s Dictum and Occam’s Razor

A recent study explored the phenomenon of multiple diagnoses by examining the supposed conflict between Hickam’s dictum and Occam’s razor, as well as the ambiguities in how they are interpreted and used by physicians in clinical reasoning.

Part 1: Researchers identified articles on PubMed related to Hickam’s dictum or conflicting with Occam’s razor, categorizing instances into four models of Hickam’s dictum:

1. Incidentaloma: An asymptomatic condition discovered accidentally.

2. Preexisting diagnosis: A known condition in the patient’s medical history.

3. Causally related disease: A complication, association, epiphenomenon, or underlying cause connected to the primary diagnosis.

4. Coincidental and independent disease: A symptomatic condition unrelated to the primary diagnosis.

Part 2: Researchers analyzed 220 case records from Massachusetts General Hospital, Boston, and clinical problem-solving reports published in The New England Journal of Medicine between 2017 and 2023. They found no cases where the final diagnosis was not a unifying one.

Part 3: In an online survey of 265 physicians, 79% identified coincidental symptomatic conditions (category 4) as the least likely type of multiple diagnoses. Preexisting conditions (category 2) emerged as the most common, reflecting the tendency to add new diagnoses to a patient’s existing health profile. Almost one third of instances referencing Hickam’s dictum or violations of Occam’s razor fell into category 2.

Causally related diseases (category 3) were probabilistically dependent, meaning that the presence of one condition increased the likelihood of the other, based on the strength (often unknown) of the causal relationship.

 

Practical Insights

The significant finding of this work was that multiple diagnoses occur in predictable patterns, informed by causal connections between conditions, symptom onset timing, and likelihood. The principle of common causation supports the search for a unifying diagnosis for coincidental symptoms. It is not surprising that causally related phenomena often co-occur, as reflected by the fact that 40% of multiple diagnoses in the study’s first part were causally linked.

Thus, understanding multiple diagnoses goes beyond Hickam’s dictum and Occam’s razor. It requires not only identifying diseases but also examining their causal relationships and the timing of symptom onset. A unifying diagnosis is not equivalent to a single diagnosis; rather, it represents a causal pathway linking underlying pathologic changes to acute presentations.

 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The principle of parsimony, often referred to as “Occam’s razor,” favors a unifying explanation over multiple ones, as long as both explain the data equally well. This heuristic, widely used in medical practice, advocates for simpler explanations rather than complex theories. However, its application in modern medicine has sparked debate.

“Hickam’s dictum,” a counterargument to Occam’s razor, asserts that patients — especially as populations grow older and more fragile — can simultaneously have multiple, unrelated diagnoses. These contrasting perspectives on clinical reasoning, balancing diagnostic simplicity and complexity, are both used in daily medical practice.

But are these two axioms truly in conflict, or is this a false dichotomy?

 

Occam’s Razor and Simple Diagnoses

Interpersonal variability in diagnostic approaches, shaped by the subjective nature of many judgments, complicates the formal evaluation of diagnostic parsimony (Occam’s razor). Indirect evidence suggests that prioritizing simplicity in diagnosis can result in under-detection of secondary conditions, particularly in patients with chronic illnesses.

For example, older patients with a known chronic illness were found to have a 30%-60% lower likelihood of being treated for an unrelated secondary diagnosis than matched peers without the chronic condition. Other studies indicate that a readily available, simple diagnosis can lead clinicians to prematurely close their diagnostic reasoning, overlooking other significant illnesses.

 

Beyond Hickam’s Dictum and Occam’s Razor

A recent study explored the phenomenon of multiple diagnoses by examining the supposed conflict between Hickam’s dictum and Occam’s razor, as well as the ambiguities in how they are interpreted and used by physicians in clinical reasoning.

Part 1: Researchers identified articles on PubMed related to Hickam’s dictum or conflicting with Occam’s razor, categorizing instances into four models of Hickam’s dictum:

1. Incidentaloma: An asymptomatic condition discovered accidentally.

2. Preexisting diagnosis: A known condition in the patient’s medical history.

3. Causally related disease: A complication, association, epiphenomenon, or underlying cause connected to the primary diagnosis.

4. Coincidental and independent disease: A symptomatic condition unrelated to the primary diagnosis.

Part 2: Researchers analyzed 220 case records from Massachusetts General Hospital, Boston, and clinical problem-solving reports published in The New England Journal of Medicine between 2017 and 2023. They found no cases where the final diagnosis was not a unifying one.

Part 3: In an online survey of 265 physicians, 79% identified coincidental symptomatic conditions (category 4) as the least likely type of multiple diagnoses. Preexisting conditions (category 2) emerged as the most common, reflecting the tendency to add new diagnoses to a patient’s existing health profile. Almost one third of instances referencing Hickam’s dictum or violations of Occam’s razor fell into category 2.

Causally related diseases (category 3) were probabilistically dependent, meaning that the presence of one condition increased the likelihood of the other, based on the strength (often unknown) of the causal relationship.

 

Practical Insights

The significant finding of this work was that multiple diagnoses occur in predictable patterns, informed by causal connections between conditions, symptom onset timing, and likelihood. The principle of common causation supports the search for a unifying diagnosis for coincidental symptoms. It is not surprising that causally related phenomena often co-occur, as reflected by the fact that 40% of multiple diagnoses in the study’s first part were causally linked.

Thus, understanding multiple diagnoses goes beyond Hickam’s dictum and Occam’s razor. It requires not only identifying diseases but also examining their causal relationships and the timing of symptom onset. A unifying diagnosis is not equivalent to a single diagnosis; rather, it represents a causal pathway linking underlying pathologic changes to acute presentations.

 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The principle of parsimony, often referred to as “Occam’s razor,” favors a unifying explanation over multiple ones, as long as both explain the data equally well. This heuristic, widely used in medical practice, advocates for simpler explanations rather than complex theories. However, its application in modern medicine has sparked debate.

“Hickam’s dictum,” a counterargument to Occam’s razor, asserts that patients — especially as populations grow older and more fragile — can simultaneously have multiple, unrelated diagnoses. These contrasting perspectives on clinical reasoning, balancing diagnostic simplicity and complexity, are both used in daily medical practice.

But are these two axioms truly in conflict, or is this a false dichotomy?

 

Occam’s Razor and Simple Diagnoses

Interpersonal variability in diagnostic approaches, shaped by the subjective nature of many judgments, complicates the formal evaluation of diagnostic parsimony (Occam’s razor). Indirect evidence suggests that prioritizing simplicity in diagnosis can result in under-detection of secondary conditions, particularly in patients with chronic illnesses.

For example, older patients with a known chronic illness were found to have a 30%-60% lower likelihood of being treated for an unrelated secondary diagnosis than matched peers without the chronic condition. Other studies indicate that a readily available, simple diagnosis can lead clinicians to prematurely close their diagnostic reasoning, overlooking other significant illnesses.

 

Beyond Hickam’s Dictum and Occam’s Razor

A recent study explored the phenomenon of multiple diagnoses by examining the supposed conflict between Hickam’s dictum and Occam’s razor, as well as the ambiguities in how they are interpreted and used by physicians in clinical reasoning.

Part 1: Researchers identified articles on PubMed related to Hickam’s dictum or conflicting with Occam’s razor, categorizing instances into four models of Hickam’s dictum:

1. Incidentaloma: An asymptomatic condition discovered accidentally.

2. Preexisting diagnosis: A known condition in the patient’s medical history.

3. Causally related disease: A complication, association, epiphenomenon, or underlying cause connected to the primary diagnosis.

4. Coincidental and independent disease: A symptomatic condition unrelated to the primary diagnosis.

Part 2: Researchers analyzed 220 case records from Massachusetts General Hospital, Boston, and clinical problem-solving reports published in The New England Journal of Medicine between 2017 and 2023. They found no cases where the final diagnosis was not a unifying one.

Part 3: In an online survey of 265 physicians, 79% identified coincidental symptomatic conditions (category 4) as the least likely type of multiple diagnoses. Preexisting conditions (category 2) emerged as the most common, reflecting the tendency to add new diagnoses to a patient’s existing health profile. Almost one third of instances referencing Hickam’s dictum or violations of Occam’s razor fell into category 2.

Causally related diseases (category 3) were probabilistically dependent, meaning that the presence of one condition increased the likelihood of the other, based on the strength (often unknown) of the causal relationship.

 

Practical Insights

The significant finding of this work was that multiple diagnoses occur in predictable patterns, informed by causal connections between conditions, symptom onset timing, and likelihood. The principle of common causation supports the search for a unifying diagnosis for coincidental symptoms. It is not surprising that causally related phenomena often co-occur, as reflected by the fact that 40% of multiple diagnoses in the study’s first part were causally linked.

Thus, understanding multiple diagnoses goes beyond Hickam’s dictum and Occam’s razor. It requires not only identifying diseases but also examining their causal relationships and the timing of symptom onset. A unifying diagnosis is not equivalent to a single diagnosis; rather, it represents a causal pathway linking underlying pathologic changes to acute presentations.

 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The use of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), is not associated with an increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes, obesity, or both conditions.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the TriNetX Analytics Network to investigate the potential risk for NAION associated with semaglutide use in a broader population worldwide.
• They included Caucasians aged ≥ 18 years with only type 2 diabetes (n = 37,245) , only obesity (n = 138,391), or both (n = 64,989) who visited healthcare facilities three or more times.
• The participants were further grouped into those prescribed semaglutide and those using non–GLP-1 RA medications.
• Propensity score matching was performed to balance age, sex, body mass index, A1C levels, medications, and underlying comorbidities between the participants using semaglutide or non–GLP-1 RAs.
• The main outcome measure was the occurrence of NAION, evaluated at 1, 2, and 3 years of follow-up.

TAKEAWAY:

• The use of semaglutide vs non–GLP-1 RAs was not associated with an increased risk for NAION in people with only type 2 diabetes during the 1-year (hazard ratio [HR], 2.32; 95% CI, 0.60-8.97), 2-year (HR, 2.31; 95% CI, 0.86-6.17), and 3-year (HR, 1.51; 0.71-3.25) follow-up periods.
• Similarly, in the obesity-only cohort, use of semaglutide was not linked to the development of NAION across 1-year (HR, 0.41; 95% CI, 0.08-2.09), 2-year (HR, 0.67; 95% CI, 0.20-2.24), and 3-year (HR, 0.72; 95% CI, 0.24-2.17) follow-up periods.
• The patients with both diabetes and obesity also showed no significant association between use of semaglutide and the risk for NAION across each follow-up period.
• Sensitivity analysis confirmed the prescription of semaglutide was not associated with an increased risk for NAION compared with non–GLP-1 RA medications.

IN PRACTICE:

“Our large, multinational, population-based, real-world study found that semaglutide is not associated with an increased risk of NAION in the general population,” the authors of the study wrote.

SOURCE:

The study was led by Chien-Chih Chou, MD, PhD, of National Yang Ming Chiao Tung University, in Taipei City, Taiwan, and was published online on November 02, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between the use of semaglutide and the risk for NAION. The reliance on diagnosis coding for NAION may have introduced a potential misclassification of cases. Moreover, approximately half of the healthcare organizations in the TriNetX network are based in the United States, potentially limiting the diversity of the data.

DISCLOSURES:

This study was supported by a grant from Taichung Veterans General Hospital. The authors declared no potential conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The use of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), is not associated with an increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes, obesity, or both conditions.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the TriNetX Analytics Network to investigate the potential risk for NAION associated with semaglutide use in a broader population worldwide.
• They included Caucasians aged ≥ 18 years with only type 2 diabetes (n = 37,245) , only obesity (n = 138,391), or both (n = 64,989) who visited healthcare facilities three or more times.
• The participants were further grouped into those prescribed semaglutide and those using non–GLP-1 RA medications.
• Propensity score matching was performed to balance age, sex, body mass index, A1C levels, medications, and underlying comorbidities between the participants using semaglutide or non–GLP-1 RAs.
• The main outcome measure was the occurrence of NAION, evaluated at 1, 2, and 3 years of follow-up.

TAKEAWAY:

• The use of semaglutide vs non–GLP-1 RAs was not associated with an increased risk for NAION in people with only type 2 diabetes during the 1-year (hazard ratio [HR], 2.32; 95% CI, 0.60-8.97), 2-year (HR, 2.31; 95% CI, 0.86-6.17), and 3-year (HR, 1.51; 0.71-3.25) follow-up periods.
• Similarly, in the obesity-only cohort, use of semaglutide was not linked to the development of NAION across 1-year (HR, 0.41; 95% CI, 0.08-2.09), 2-year (HR, 0.67; 95% CI, 0.20-2.24), and 3-year (HR, 0.72; 95% CI, 0.24-2.17) follow-up periods.
• The patients with both diabetes and obesity also showed no significant association between use of semaglutide and the risk for NAION across each follow-up period.
• Sensitivity analysis confirmed the prescription of semaglutide was not associated with an increased risk for NAION compared with non–GLP-1 RA medications.

IN PRACTICE:

“Our large, multinational, population-based, real-world study found that semaglutide is not associated with an increased risk of NAION in the general population,” the authors of the study wrote.

SOURCE:

The study was led by Chien-Chih Chou, MD, PhD, of National Yang Ming Chiao Tung University, in Taipei City, Taiwan, and was published online on November 02, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between the use of semaglutide and the risk for NAION. The reliance on diagnosis coding for NAION may have introduced a potential misclassification of cases. Moreover, approximately half of the healthcare organizations in the TriNetX network are based in the United States, potentially limiting the diversity of the data.

DISCLOSURES:

This study was supported by a grant from Taichung Veterans General Hospital. The authors declared no potential conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The use of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), is not associated with an increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes, obesity, or both conditions.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the TriNetX Analytics Network to investigate the potential risk for NAION associated with semaglutide use in a broader population worldwide.
• They included Caucasians aged ≥ 18 years with only type 2 diabetes (n = 37,245) , only obesity (n = 138,391), or both (n = 64,989) who visited healthcare facilities three or more times.
• The participants were further grouped into those prescribed semaglutide and those using non–GLP-1 RA medications.
• Propensity score matching was performed to balance age, sex, body mass index, A1C levels, medications, and underlying comorbidities between the participants using semaglutide or non–GLP-1 RAs.
• The main outcome measure was the occurrence of NAION, evaluated at 1, 2, and 3 years of follow-up.

TAKEAWAY:

• The use of semaglutide vs non–GLP-1 RAs was not associated with an increased risk for NAION in people with only type 2 diabetes during the 1-year (hazard ratio [HR], 2.32; 95% CI, 0.60-8.97), 2-year (HR, 2.31; 95% CI, 0.86-6.17), and 3-year (HR, 1.51; 0.71-3.25) follow-up periods.
• Similarly, in the obesity-only cohort, use of semaglutide was not linked to the development of NAION across 1-year (HR, 0.41; 95% CI, 0.08-2.09), 2-year (HR, 0.67; 95% CI, 0.20-2.24), and 3-year (HR, 0.72; 95% CI, 0.24-2.17) follow-up periods.
• The patients with both diabetes and obesity also showed no significant association between use of semaglutide and the risk for NAION across each follow-up period.
• Sensitivity analysis confirmed the prescription of semaglutide was not associated with an increased risk for NAION compared with non–GLP-1 RA medications.

IN PRACTICE:

“Our large, multinational, population-based, real-world study found that semaglutide is not associated with an increased risk of NAION in the general population,” the authors of the study wrote.

SOURCE:

The study was led by Chien-Chih Chou, MD, PhD, of National Yang Ming Chiao Tung University, in Taipei City, Taiwan, and was published online on November 02, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between the use of semaglutide and the risk for NAION. The reliance on diagnosis coding for NAION may have introduced a potential misclassification of cases. Moreover, approximately half of the healthcare organizations in the TriNetX network are based in the United States, potentially limiting the diversity of the data.

DISCLOSURES:

This study was supported by a grant from Taichung Veterans General Hospital. The authors declared no potential conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Consumption of ultraprocessed foods (UPFs), such as carbonated drinks, processed meats, and sweet or savory packaged snacks, is associated with accelerated biological aging, as measured by 36 blood-based biomarkers, and factors other than poor nutritional content may be to blame.

METHODOLOGY:

• Previous studies have reported an association between high consumption of UPFs and some measures of early biological aging, such as shorter telomere length, cognitive decline, and frailty, but the relationship is largely unexplored so far, including exactly how UPFs may harm health.
• To examine the association between UPF consumption and biological aging, researchers conducted a cross-sectional analysis of 22,495 participants (mean chronological age, 55.6 years; 52% women) from the Moli-sani Study in Italy, who were recruited between 2005 and 2010.
• Food intake was assessed with a food frequency questionnaire that covered 188 different food items, each of which was categorized into one of four groups based on the extent of processing, ranging from minimally processed foods, such as fruits, vegetables, meat and fish, to UPFs.
• UPF intake was determined by weight, using the ratio of UPFs to the total weight of food and beverages (g/d), and participants were categorized into sex-specific fifths according to the proportion of UPFs in their total food intake. Diet quality was also evaluated using the Mediterranean Diet Score.
• Biological age was computed using a deep neural network approach based on 36 circulating blood biomarkers, and the mean difference between the mean biological and chronological ages was analyzed.

TAKEAWAY:

• The mean difference between biological and chronological ages of the participants was –0.70 years.
• Higher intake of UPFs was associated with accelerated biological aging compared with the lowest intake (regression coefficient, 0.34; 95% CI, 0.08-0.61), with a mean difference between the biological and chronological ages of −4.1 years and 1.6 years in those with the lowest and highest intakes, respectively.
• The association between UPF consumption and biological aging was nonlinear (P = .049 for nonlinearity). The association tended to be stronger in men than in women, but this was not statistically significant.
• Including the Mediterranean Diet Score in the model slightly attenuated the association by 9.1%, indicating that poor nutritional content was likely to explain a small part of the underlying mechanism.

IN PRACTICE:

“Our results showed that the UPFs–biological aging association was weakly explained by the poor nutritional composition of these highly processed foods, suggesting that biological aging could be mainly influenced by non-nutrient food characteristics, which include altered food matrix, contact materials and neo-formed compounds,” the authors wrote.

 

SOURCE:

The study was led by Simona Esposito, Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Isernia, Italy. It was published online in The American Journal of Clinical Nutrition.

 

LIMITATIONS:

The cross-sectional design of the study limited the ability to determine the temporal directionality of the association, and the observational nature of the study limited the ability to establish the causality between UPF consumption and biological aging. The use of self-reported dietary data may have introduced recall bias. The study population was limited to adults from Central-Southern Italy, which may affect the generalizability of the findings.

 

DISCLOSURES:

The study was developed within the project funded by the Next Generation European Union “Age-It — Ageing well in an ageing society” project, National Recovery and Resilience Plan. The analyses were partially supported by the Italian Ministry of Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Consumption of ultraprocessed foods (UPFs), such as carbonated drinks, processed meats, and sweet or savory packaged snacks, is associated with accelerated biological aging, as measured by 36 blood-based biomarkers, and factors other than poor nutritional content may be to blame.

METHODOLOGY:

• Previous studies have reported an association between high consumption of UPFs and some measures of early biological aging, such as shorter telomere length, cognitive decline, and frailty, but the relationship is largely unexplored so far, including exactly how UPFs may harm health.
• To examine the association between UPF consumption and biological aging, researchers conducted a cross-sectional analysis of 22,495 participants (mean chronological age, 55.6 years; 52% women) from the Moli-sani Study in Italy, who were recruited between 2005 and 2010.
• Food intake was assessed with a food frequency questionnaire that covered 188 different food items, each of which was categorized into one of four groups based on the extent of processing, ranging from minimally processed foods, such as fruits, vegetables, meat and fish, to UPFs.
• UPF intake was determined by weight, using the ratio of UPFs to the total weight of food and beverages (g/d), and participants were categorized into sex-specific fifths according to the proportion of UPFs in their total food intake. Diet quality was also evaluated using the Mediterranean Diet Score.
• Biological age was computed using a deep neural network approach based on 36 circulating blood biomarkers, and the mean difference between the mean biological and chronological ages was analyzed.

TAKEAWAY:

• The mean difference between biological and chronological ages of the participants was –0.70 years.
• Higher intake of UPFs was associated with accelerated biological aging compared with the lowest intake (regression coefficient, 0.34; 95% CI, 0.08-0.61), with a mean difference between the biological and chronological ages of −4.1 years and 1.6 years in those with the lowest and highest intakes, respectively.
• The association between UPF consumption and biological aging was nonlinear (P = .049 for nonlinearity). The association tended to be stronger in men than in women, but this was not statistically significant.
• Including the Mediterranean Diet Score in the model slightly attenuated the association by 9.1%, indicating that poor nutritional content was likely to explain a small part of the underlying mechanism.

IN PRACTICE:

“Our results showed that the UPFs–biological aging association was weakly explained by the poor nutritional composition of these highly processed foods, suggesting that biological aging could be mainly influenced by non-nutrient food characteristics, which include altered food matrix, contact materials and neo-formed compounds,” the authors wrote.

 

SOURCE:

The study was led by Simona Esposito, Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Isernia, Italy. It was published online in The American Journal of Clinical Nutrition.

 

LIMITATIONS:

The cross-sectional design of the study limited the ability to determine the temporal directionality of the association, and the observational nature of the study limited the ability to establish the causality between UPF consumption and biological aging. The use of self-reported dietary data may have introduced recall bias. The study population was limited to adults from Central-Southern Italy, which may affect the generalizability of the findings.

 

DISCLOSURES:

The study was developed within the project funded by the Next Generation European Union “Age-It — Ageing well in an ageing society” project, National Recovery and Resilience Plan. The analyses were partially supported by the Italian Ministry of Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Consumption of ultraprocessed foods (UPFs), such as carbonated drinks, processed meats, and sweet or savory packaged snacks, is associated with accelerated biological aging, as measured by 36 blood-based biomarkers, and factors other than poor nutritional content may be to blame.

METHODOLOGY:

• Previous studies have reported an association between high consumption of UPFs and some measures of early biological aging, such as shorter telomere length, cognitive decline, and frailty, but the relationship is largely unexplored so far, including exactly how UPFs may harm health.
• To examine the association between UPF consumption and biological aging, researchers conducted a cross-sectional analysis of 22,495 participants (mean chronological age, 55.6 years; 52% women) from the Moli-sani Study in Italy, who were recruited between 2005 and 2010.
• Food intake was assessed with a food frequency questionnaire that covered 188 different food items, each of which was categorized into one of four groups based on the extent of processing, ranging from minimally processed foods, such as fruits, vegetables, meat and fish, to UPFs.
• UPF intake was determined by weight, using the ratio of UPFs to the total weight of food and beverages (g/d), and participants were categorized into sex-specific fifths according to the proportion of UPFs in their total food intake. Diet quality was also evaluated using the Mediterranean Diet Score.
• Biological age was computed using a deep neural network approach based on 36 circulating blood biomarkers, and the mean difference between the mean biological and chronological ages was analyzed.

TAKEAWAY:

• The mean difference between biological and chronological ages of the participants was –0.70 years.
• Higher intake of UPFs was associated with accelerated biological aging compared with the lowest intake (regression coefficient, 0.34; 95% CI, 0.08-0.61), with a mean difference between the biological and chronological ages of −4.1 years and 1.6 years in those with the lowest and highest intakes, respectively.
• The association between UPF consumption and biological aging was nonlinear (P = .049 for nonlinearity). The association tended to be stronger in men than in women, but this was not statistically significant.
• Including the Mediterranean Diet Score in the model slightly attenuated the association by 9.1%, indicating that poor nutritional content was likely to explain a small part of the underlying mechanism.

IN PRACTICE:

“Our results showed that the UPFs–biological aging association was weakly explained by the poor nutritional composition of these highly processed foods, suggesting that biological aging could be mainly influenced by non-nutrient food characteristics, which include altered food matrix, contact materials and neo-formed compounds,” the authors wrote.

 

SOURCE:

The study was led by Simona Esposito, Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Isernia, Italy. It was published online in The American Journal of Clinical Nutrition.

 

LIMITATIONS:

The cross-sectional design of the study limited the ability to determine the temporal directionality of the association, and the observational nature of the study limited the ability to establish the causality between UPF consumption and biological aging. The use of self-reported dietary data may have introduced recall bias. The study population was limited to adults from Central-Southern Italy, which may affect the generalizability of the findings.

 

DISCLOSURES:

The study was developed within the project funded by the Next Generation European Union “Age-It — Ageing well in an ageing society” project, National Recovery and Resilience Plan. The analyses were partially supported by the Italian Ministry of Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.