Clinical Endocrinology News

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.

TOPLINE:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

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:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

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:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

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.

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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:

Levonorgestrel intrauterine devices (IUDs) are associated with significantly more reports of acne, alopecia, and hirsutism compared with copper IUDs, with some differences between the available levonorgestrel IUDs.

METHODOLOGY:

• Researchers reviewed the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) through December 2023 for adverse events associated with levonorgestrel IUDs where IUDs were the only suspected cause, focusing on acne, alopecia, and hirsutism.
• They included 139,348 reports for the levonorgestrel IUDs (Mirena, Liletta, Kyleena, Skyla) and 50,450 reports for the copper IUD (Paragard).

TAKEAWAY:

• Levonorgestrel IUD users showed higher odds of reporting acne (odds ratio [OR], 3.21), alopecia (OR, 5.96), and hirsutism (OR, 15.48; all P < .0001) than copper IUD users.
• The Kyleena 19.5 mg levonorgestrel IUD was associated with the highest odds of acne reports (OR, 3.42), followed by the Mirena 52 mg (OR, 3.40) and Skyla 13.5 mg (OR, 2.30) levonorgestrel IUDs (all P < .0001).
• The Mirena IUD was associated with the highest odds of alopecia and hirsutism reports (OR, 6.62 and 17.43, respectively), followed by the Kyleena (ORs, 2.90 and 8.17, respectively) and Skyla (ORs, 2.69 and 1.48, respectively) IUDs (all P < .0001).
• Reports of acne, alopecia, and hirsutism were not significantly different between the Liletta 52 mg levonorgestrel IUD and the copper IUD.

IN PRACTICE:

“Overall, we identified significant associations between levonorgestrel IUDs and androgenic cutaneous adverse events,” the authors wrote. “Counseling prior to initiation of levonorgestrel IUDs should include information on possible cutaneous AEs including acne, alopecia, and hirsutism to guide contraceptive shared decision making,” they added.

 

SOURCE:

The study was led by Lydia Cassard, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, and was published online November 3 in Journal of the American Academy of Dermatology.

LIMITATIONS:

FAERS database reports could not be verified, and differences in FDA approval dates for IUDs could have influenced reporting rates. Moreover, a lack of data on prior medication use limits the ability to determine if these AEs are a result of changes in androgenic or antiandrogenic medication use. Cutaneous adverse events associated with copper IUDs may have been underreported because of assumptions that a nonhormonal device would not cause these adverse events.

DISCLOSURES:

The authors did not report any funding source or conflict of interests.

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:

Levonorgestrel intrauterine devices (IUDs) are associated with significantly more reports of acne, alopecia, and hirsutism compared with copper IUDs, with some differences between the available levonorgestrel IUDs.

METHODOLOGY:

• Researchers reviewed the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) through December 2023 for adverse events associated with levonorgestrel IUDs where IUDs were the only suspected cause, focusing on acne, alopecia, and hirsutism.
• They included 139,348 reports for the levonorgestrel IUDs (Mirena, Liletta, Kyleena, Skyla) and 50,450 reports for the copper IUD (Paragard).

TAKEAWAY:

• Levonorgestrel IUD users showed higher odds of reporting acne (odds ratio [OR], 3.21), alopecia (OR, 5.96), and hirsutism (OR, 15.48; all P < .0001) than copper IUD users.
• The Kyleena 19.5 mg levonorgestrel IUD was associated with the highest odds of acne reports (OR, 3.42), followed by the Mirena 52 mg (OR, 3.40) and Skyla 13.5 mg (OR, 2.30) levonorgestrel IUDs (all P < .0001).
• The Mirena IUD was associated with the highest odds of alopecia and hirsutism reports (OR, 6.62 and 17.43, respectively), followed by the Kyleena (ORs, 2.90 and 8.17, respectively) and Skyla (ORs, 2.69 and 1.48, respectively) IUDs (all P < .0001).
• Reports of acne, alopecia, and hirsutism were not significantly different between the Liletta 52 mg levonorgestrel IUD and the copper IUD.

IN PRACTICE:

“Overall, we identified significant associations between levonorgestrel IUDs and androgenic cutaneous adverse events,” the authors wrote. “Counseling prior to initiation of levonorgestrel IUDs should include information on possible cutaneous AEs including acne, alopecia, and hirsutism to guide contraceptive shared decision making,” they added.

 

SOURCE:

The study was led by Lydia Cassard, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, and was published online November 3 in Journal of the American Academy of Dermatology.

LIMITATIONS:

FAERS database reports could not be verified, and differences in FDA approval dates for IUDs could have influenced reporting rates. Moreover, a lack of data on prior medication use limits the ability to determine if these AEs are a result of changes in androgenic or antiandrogenic medication use. Cutaneous adverse events associated with copper IUDs may have been underreported because of assumptions that a nonhormonal device would not cause these adverse events.

DISCLOSURES:

The authors did not report any funding source or conflict of interests.

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:

Levonorgestrel intrauterine devices (IUDs) are associated with significantly more reports of acne, alopecia, and hirsutism compared with copper IUDs, with some differences between the available levonorgestrel IUDs.

METHODOLOGY:

• Researchers reviewed the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) through December 2023 for adverse events associated with levonorgestrel IUDs where IUDs were the only suspected cause, focusing on acne, alopecia, and hirsutism.
• They included 139,348 reports for the levonorgestrel IUDs (Mirena, Liletta, Kyleena, Skyla) and 50,450 reports for the copper IUD (Paragard).

TAKEAWAY:

• Levonorgestrel IUD users showed higher odds of reporting acne (odds ratio [OR], 3.21), alopecia (OR, 5.96), and hirsutism (OR, 15.48; all P < .0001) than copper IUD users.
• The Kyleena 19.5 mg levonorgestrel IUD was associated with the highest odds of acne reports (OR, 3.42), followed by the Mirena 52 mg (OR, 3.40) and Skyla 13.5 mg (OR, 2.30) levonorgestrel IUDs (all P < .0001).
• The Mirena IUD was associated with the highest odds of alopecia and hirsutism reports (OR, 6.62 and 17.43, respectively), followed by the Kyleena (ORs, 2.90 and 8.17, respectively) and Skyla (ORs, 2.69 and 1.48, respectively) IUDs (all P < .0001).
• Reports of acne, alopecia, and hirsutism were not significantly different between the Liletta 52 mg levonorgestrel IUD and the copper IUD.

IN PRACTICE:

“Overall, we identified significant associations between levonorgestrel IUDs and androgenic cutaneous adverse events,” the authors wrote. “Counseling prior to initiation of levonorgestrel IUDs should include information on possible cutaneous AEs including acne, alopecia, and hirsutism to guide contraceptive shared decision making,” they added.

 

SOURCE:

The study was led by Lydia Cassard, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, and was published online November 3 in Journal of the American Academy of Dermatology.

LIMITATIONS:

FAERS database reports could not be verified, and differences in FDA approval dates for IUDs could have influenced reporting rates. Moreover, a lack of data on prior medication use limits the ability to determine if these AEs are a result of changes in androgenic or antiandrogenic medication use. Cutaneous adverse events associated with copper IUDs may have been underreported because of assumptions that a nonhormonal device would not cause these adverse events.

DISCLOSURES:

The authors did not report any funding source or conflict of interests.

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:

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.