Obesity

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

The majority of patients may safely take glucagon-like peptide 1 receptor agonists (GLP-1 RAs) before elective surgery and gastrointestinal endoscopies, according to updated guidance from five medical societies.

The new guidance, contrasting with earlier recommendations, says these incrementally used agents can be taken up until the day of surgery, but patients are advised to follow a liquid diet for 24 hours before the procedure. The decision to proceed with endoscopy and other procedures should be based on shared decision-making with the patient and interdisciplinary care teams in conjunction with minimization of the aspiration risk from delayed gastric emptying, the guidance stresses.

The five endorsing organizations are the American Society for Metabolic and Bariatric Surgery, American Society of Anesthesiologists (ASA), American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons. The societies emphasize that the statement is intended as guidance only and is not an evidence-based formal guideline.

GLP-1 RAs are known to delay gastric emptying, raising concerns about regurgitation, aspiration, and airway compromise during anesthesia. Rare serious adverse events have also been observed, prompting the ASA in 2023 to recommend holding these agents for 1 week for the injectable form and 1 day for the oral form before all procedures requiring anesthesia. 

 

University of Michigan

That abundance of caution, however, had negative impacts of its own. “This guidance has led to cancellations and postponements of many endoscopic and surgical procedures or required patients to undergo general anesthesia who may otherwise have had their procedures performed under moderate sedation,” said guidance coauthor Allison R. Schulman, MD, MPH, an associate professor of medicine and surgery and chief of endoscopy at the University of Michigan in Ann Arbor. “Nearly all institutions have been forced to revise preprocedural protocols, despite a lack of high-level evidence to suggest that these adjustments are necessary.”

“Studies have yielded mixed results as to whether patients on GLP-1s are at increased risk of these events, and the limited data available are inconsistent,” Schulman said. “As a result, there are inconsistencies in the recommendations from various societies leading to growing uncertainty with proceduralists on how to provide safe, effective, and timely procedural care to patients taking GLP-1 RAs.”

The new joint-society guidance may alleviate some of the uncertainty. Among the recommendations:

• Continuing GLP-1 RAs in the perioperative period should be based on shared decision-making with the patient and all care teams balancing the metabolic need for the GLP-1 RA with individual patient risk.
• Certain variables may increase the risk for delayed gastric emptying and aspiration with the periprocedural use of GLP-1 RAs: escalation phase — This phase vs the maintenance phase is associated with a higher risk for delayed gastric emptying; higher dose — the higher the dose, the greater the risk for gastrointestinal (GI) side effects; weekly dosing — GI side effects are more common with weekly vs daily formulations; presence of GI symptoms — nausea, vomiting, abdominal pain, dyspepsia, and constipation may suggest delayed gastric emptying; and medical problems beyond GLP-1 RA indications with GI effects — assess for such conditions as bowel dysmotility, gastroparesis, and Parkinson’s disease.
• Risk factors should be assessed in advance to allow sufficient time to adjust preoperative care, including diet modification and medication bridging if GLP-1 RA cessation is deemed advisable.
• If retained gastric contents are a concern on the day of a procedure, point-of-care gastric ultrasound could be used to assess aspiration risk, resources permitting.
• The aspiration risk from delayed gastric emptying should be minimized by preoperative diet modification and/or altering the anesthesia plan to consider rapid sequence induction of general anesthesia for tracheal intubation. A 24-hour preoperative liquid diet, as before colonoscopy and bariatric surgery, can be utilized when delayed gastric emptying is a concern.
• When concern about retained gastric contents exists on procedure day, providers should engage patients in a shared decision-making model and consider the benefits and risks of rapid-sequence induction of general anesthesia for tracheal intubation to minimize aspiration risk vs procedure cancellation.

“Safe continuation of surgery and gastrointestinal endoscopy, and prevention of procedure cancellation, for patients on GLP-1 RAs can be prioritized following the recommendations above, as would occur for other patient populations with gastroparesis,” the guidance panel wrote.

 

Digestive Health Center of Huntington

Commenting on the statement but not involved in it, David B. Purow, MD, managing director of the Digestive Health Center at Northwell Health/Huntington Hospital in Huntington, New York, said the recommendations will encourage clinicians to be more discerning about actual risk in individual cases rather than follow the previous blanket recommendation to stop these agents before procedures requiring sedation. 

While GLP-1 RAs were prescribed for the relatively small number of patients with diabetes, he said, the risk was not apparent but became clearer with the widespread use of these agents for weight loss — often unregulated and undisclosed to care providers.

“The pendulum shifted too far the other way, and now it’s shifted back,” he said in an interview. “The new guidance is great because now we can be more thoughtful about managing individual patients.” He cited, for instance, the recommendations on the greater risk in patients in the dose escalation phase or on higher doses, and the risk-reducing measure of a liquid diet for 24 hours before surgery.

His center is already using point-of-care ultrasound and recently had a case in which a patient who forgot and took his GLP-1 RA before a scheduled procedure was found on ultrasound to have a full stomach. “In some cases, these drugs can cause an almost gastroparesis level of delayed emptying,” Purow said.

Purow thinks this early guidance will probably progress to firm guidelines within a year. Schulman is more cautious. “Our understanding of this complex topic is increasing rapidly, and ongoing clinical research will ultimately lead to evidence-based guidelines in this changing landscape,” she said.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Schulman is a consultant for Apollo Endosurgery, Boston Scientific, Olympus, Microtech, and Fractyl. Purow had no competing interests to declare.

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

The majority of patients may safely take glucagon-like peptide 1 receptor agonists (GLP-1 RAs) before elective surgery and gastrointestinal endoscopies, according to updated guidance from five medical societies.

The new guidance, contrasting with earlier recommendations, says these incrementally used agents can be taken up until the day of surgery, but patients are advised to follow a liquid diet for 24 hours before the procedure. The decision to proceed with endoscopy and other procedures should be based on shared decision-making with the patient and interdisciplinary care teams in conjunction with minimization of the aspiration risk from delayed gastric emptying, the guidance stresses.

The five endorsing organizations are the American Society for Metabolic and Bariatric Surgery, American Society of Anesthesiologists (ASA), American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons. The societies emphasize that the statement is intended as guidance only and is not an evidence-based formal guideline.

GLP-1 RAs are known to delay gastric emptying, raising concerns about regurgitation, aspiration, and airway compromise during anesthesia. Rare serious adverse events have also been observed, prompting the ASA in 2023 to recommend holding these agents for 1 week for the injectable form and 1 day for the oral form before all procedures requiring anesthesia. 

 

University of Michigan

That abundance of caution, however, had negative impacts of its own. “This guidance has led to cancellations and postponements of many endoscopic and surgical procedures or required patients to undergo general anesthesia who may otherwise have had their procedures performed under moderate sedation,” said guidance coauthor Allison R. Schulman, MD, MPH, an associate professor of medicine and surgery and chief of endoscopy at the University of Michigan in Ann Arbor. “Nearly all institutions have been forced to revise preprocedural protocols, despite a lack of high-level evidence to suggest that these adjustments are necessary.”

“Studies have yielded mixed results as to whether patients on GLP-1s are at increased risk of these events, and the limited data available are inconsistent,” Schulman said. “As a result, there are inconsistencies in the recommendations from various societies leading to growing uncertainty with proceduralists on how to provide safe, effective, and timely procedural care to patients taking GLP-1 RAs.”

The new joint-society guidance may alleviate some of the uncertainty. Among the recommendations:

• Continuing GLP-1 RAs in the perioperative period should be based on shared decision-making with the patient and all care teams balancing the metabolic need for the GLP-1 RA with individual patient risk.
• Certain variables may increase the risk for delayed gastric emptying and aspiration with the periprocedural use of GLP-1 RAs: escalation phase — This phase vs the maintenance phase is associated with a higher risk for delayed gastric emptying; higher dose — the higher the dose, the greater the risk for gastrointestinal (GI) side effects; weekly dosing — GI side effects are more common with weekly vs daily formulations; presence of GI symptoms — nausea, vomiting, abdominal pain, dyspepsia, and constipation may suggest delayed gastric emptying; and medical problems beyond GLP-1 RA indications with GI effects — assess for such conditions as bowel dysmotility, gastroparesis, and Parkinson’s disease.
• Risk factors should be assessed in advance to allow sufficient time to adjust preoperative care, including diet modification and medication bridging if GLP-1 RA cessation is deemed advisable.
• If retained gastric contents are a concern on the day of a procedure, point-of-care gastric ultrasound could be used to assess aspiration risk, resources permitting.
• The aspiration risk from delayed gastric emptying should be minimized by preoperative diet modification and/or altering the anesthesia plan to consider rapid sequence induction of general anesthesia for tracheal intubation. A 24-hour preoperative liquid diet, as before colonoscopy and bariatric surgery, can be utilized when delayed gastric emptying is a concern.
• When concern about retained gastric contents exists on procedure day, providers should engage patients in a shared decision-making model and consider the benefits and risks of rapid-sequence induction of general anesthesia for tracheal intubation to minimize aspiration risk vs procedure cancellation.

“Safe continuation of surgery and gastrointestinal endoscopy, and prevention of procedure cancellation, for patients on GLP-1 RAs can be prioritized following the recommendations above, as would occur for other patient populations with gastroparesis,” the guidance panel wrote.

 

Digestive Health Center of Huntington

Commenting on the statement but not involved in it, David B. Purow, MD, managing director of the Digestive Health Center at Northwell Health/Huntington Hospital in Huntington, New York, said the recommendations will encourage clinicians to be more discerning about actual risk in individual cases rather than follow the previous blanket recommendation to stop these agents before procedures requiring sedation. 

While GLP-1 RAs were prescribed for the relatively small number of patients with diabetes, he said, the risk was not apparent but became clearer with the widespread use of these agents for weight loss — often unregulated and undisclosed to care providers.

“The pendulum shifted too far the other way, and now it’s shifted back,” he said in an interview. “The new guidance is great because now we can be more thoughtful about managing individual patients.” He cited, for instance, the recommendations on the greater risk in patients in the dose escalation phase or on higher doses, and the risk-reducing measure of a liquid diet for 24 hours before surgery.

His center is already using point-of-care ultrasound and recently had a case in which a patient who forgot and took his GLP-1 RA before a scheduled procedure was found on ultrasound to have a full stomach. “In some cases, these drugs can cause an almost gastroparesis level of delayed emptying,” Purow said.

Purow thinks this early guidance will probably progress to firm guidelines within a year. Schulman is more cautious. “Our understanding of this complex topic is increasing rapidly, and ongoing clinical research will ultimately lead to evidence-based guidelines in this changing landscape,” she said.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Schulman is a consultant for Apollo Endosurgery, Boston Scientific, Olympus, Microtech, and Fractyl. Purow had no competing interests to declare.

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

The majority of patients may safely take glucagon-like peptide 1 receptor agonists (GLP-1 RAs) before elective surgery and gastrointestinal endoscopies, according to updated guidance from five medical societies.

The new guidance, contrasting with earlier recommendations, says these incrementally used agents can be taken up until the day of surgery, but patients are advised to follow a liquid diet for 24 hours before the procedure. The decision to proceed with endoscopy and other procedures should be based on shared decision-making with the patient and interdisciplinary care teams in conjunction with minimization of the aspiration risk from delayed gastric emptying, the guidance stresses.

The five endorsing organizations are the American Society for Metabolic and Bariatric Surgery, American Society of Anesthesiologists (ASA), American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons. The societies emphasize that the statement is intended as guidance only and is not an evidence-based formal guideline.

GLP-1 RAs are known to delay gastric emptying, raising concerns about regurgitation, aspiration, and airway compromise during anesthesia. Rare serious adverse events have also been observed, prompting the ASA in 2023 to recommend holding these agents for 1 week for the injectable form and 1 day for the oral form before all procedures requiring anesthesia. 

 

University of Michigan

That abundance of caution, however, had negative impacts of its own. “This guidance has led to cancellations and postponements of many endoscopic and surgical procedures or required patients to undergo general anesthesia who may otherwise have had their procedures performed under moderate sedation,” said guidance coauthor Allison R. Schulman, MD, MPH, an associate professor of medicine and surgery and chief of endoscopy at the University of Michigan in Ann Arbor. “Nearly all institutions have been forced to revise preprocedural protocols, despite a lack of high-level evidence to suggest that these adjustments are necessary.”

“Studies have yielded mixed results as to whether patients on GLP-1s are at increased risk of these events, and the limited data available are inconsistent,” Schulman said. “As a result, there are inconsistencies in the recommendations from various societies leading to growing uncertainty with proceduralists on how to provide safe, effective, and timely procedural care to patients taking GLP-1 RAs.”

The new joint-society guidance may alleviate some of the uncertainty. Among the recommendations:

• Continuing GLP-1 RAs in the perioperative period should be based on shared decision-making with the patient and all care teams balancing the metabolic need for the GLP-1 RA with individual patient risk.
• Certain variables may increase the risk for delayed gastric emptying and aspiration with the periprocedural use of GLP-1 RAs: escalation phase — This phase vs the maintenance phase is associated with a higher risk for delayed gastric emptying; higher dose — the higher the dose, the greater the risk for gastrointestinal (GI) side effects; weekly dosing — GI side effects are more common with weekly vs daily formulations; presence of GI symptoms — nausea, vomiting, abdominal pain, dyspepsia, and constipation may suggest delayed gastric emptying; and medical problems beyond GLP-1 RA indications with GI effects — assess for such conditions as bowel dysmotility, gastroparesis, and Parkinson’s disease.
• Risk factors should be assessed in advance to allow sufficient time to adjust preoperative care, including diet modification and medication bridging if GLP-1 RA cessation is deemed advisable.
• If retained gastric contents are a concern on the day of a procedure, point-of-care gastric ultrasound could be used to assess aspiration risk, resources permitting.
• The aspiration risk from delayed gastric emptying should be minimized by preoperative diet modification and/or altering the anesthesia plan to consider rapid sequence induction of general anesthesia for tracheal intubation. A 24-hour preoperative liquid diet, as before colonoscopy and bariatric surgery, can be utilized when delayed gastric emptying is a concern.
• When concern about retained gastric contents exists on procedure day, providers should engage patients in a shared decision-making model and consider the benefits and risks of rapid-sequence induction of general anesthesia for tracheal intubation to minimize aspiration risk vs procedure cancellation.

“Safe continuation of surgery and gastrointestinal endoscopy, and prevention of procedure cancellation, for patients on GLP-1 RAs can be prioritized following the recommendations above, as would occur for other patient populations with gastroparesis,” the guidance panel wrote.

 

Digestive Health Center of Huntington

Commenting on the statement but not involved in it, David B. Purow, MD, managing director of the Digestive Health Center at Northwell Health/Huntington Hospital in Huntington, New York, said the recommendations will encourage clinicians to be more discerning about actual risk in individual cases rather than follow the previous blanket recommendation to stop these agents before procedures requiring sedation. 

While GLP-1 RAs were prescribed for the relatively small number of patients with diabetes, he said, the risk was not apparent but became clearer with the widespread use of these agents for weight loss — often unregulated and undisclosed to care providers.

“The pendulum shifted too far the other way, and now it’s shifted back,” he said in an interview. “The new guidance is great because now we can be more thoughtful about managing individual patients.” He cited, for instance, the recommendations on the greater risk in patients in the dose escalation phase or on higher doses, and the risk-reducing measure of a liquid diet for 24 hours before surgery.

His center is already using point-of-care ultrasound and recently had a case in which a patient who forgot and took his GLP-1 RA before a scheduled procedure was found on ultrasound to have a full stomach. “In some cases, these drugs can cause an almost gastroparesis level of delayed emptying,” Purow said.

Purow thinks this early guidance will probably progress to firm guidelines within a year. Schulman is more cautious. “Our understanding of this complex topic is increasing rapidly, and ongoing clinical research will ultimately lead to evidence-based guidelines in this changing landscape,” she said.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Schulman is a consultant for Apollo Endosurgery, Boston Scientific, Olympus, Microtech, and Fractyl. Purow had no competing interests to declare.

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

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported 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 first appeared on Medscape.com.

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported 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 first appeared on Medscape.com.

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported 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 first appeared on Medscape.com.

SAN ANTONIO — Despite the prevalence of obesity in primary care, there appear to be major knowledge gaps among providers regarding obesity management, new research suggests. 

Anonymous surveys of 96 primary care providers at a Boston, Massachusetts, safety-net hospital revealed that participants had limited understanding of criteria for prescribing antiobesity medications (AOM), and expressed discomfort in prescribing AOMs because of knowledge concerns, especially for non–glucagon-like peptide 1 (GLP-1) receptor agonists. One third reported that they didn’t prescribe AOMs, and rates of referral for bariatric surgery were also low. 

The findings were presented at the Obesity Society’s annual Obesity Week meeting by Alejandro Campos, MD, a third-year resident in the section of internal medicine, Boston Medical Center, and the Department of Medicine, Boston University. 

“I think it comes down to education. ... Not only training primary care physicians or residents about criteria and pathophysiology, but also stigma. Perceptions need to be addressed from the start of training in the healthcare field,” Campos told this news organization in an interview.

During his presentation, Campos noted this is the first such study in the setting of a safety-net hospital, which cares for lower-income people who experience disproportionate rates of obesity. But, “these findings are similar to ones observed from non–safety-net settings, which can indicate some potential transferability.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, told this news organization that the findings didn’t surprise him. “I’d say that medical education around obesity has definitely improved, and training is improving but it’s not uniform. The treatment of obesity as a disease, especially with some of the newer medical treatments, is not standard of care and practiced widely.”

The study involved a standard-model Knowledge, Attitudes, and Practices questionnaire, distributed electronically for anonymous responses among both trained and in-training primary care providers. It contained a total of 43 items, 7 of them demographic, 11 on knowledge, 9 regarding attitudes, and 16 asking about practices.

The hospital is the largest safety-net hospital in New England, with a patient population that includes 58% enrolled in Medicaid, 32% Black/African American individuals, 24% identifying as Hispanic/Latino individuals, and 37% living below the poverty line.

The 96 responding providers (from a total 350 invited) all worked in either family medicine or internal medicine. The trained providers included both attending MDs and nurse practitioners, while those in-training were residents in one of those two specialties. Two thirds were women. The majority were aged 20-30 years (49.45%) or 31-40 years (27.47%).

Overall, 73.63% reported having received some type of obesity training. Just over half (52.08%) reported receiving that training during medical or nursing school, while 43.75% reported receiving it during residency.

When asked to choose from a list of conditions to pick which are considered weight-related comorbidities, between 80% and 90% choose type 2 diabetes, obstructive sleep apnea (OSA), hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. Fewer, but still a majority, also listed osteoarthritis and gastroesophageal reflux disease. However, respondents were less likely to cite cancer, mood disorders, or chronic kidney disease as being related to obesity.

Asked to list benefits of a 10% body weight loss, most recognized reductions in OSA, glycemia, cardiovascular disease risk, osteoarthritis, and hepatic steatosis. But, only about half knew weight loss could also improve urinary incontinence.

Only 25% could correctly name both indications for AOMs. Just 27.1% knew that one was a body mass index (BMI) ≥ 27 with comorbidities, while 46.9% knew BMI ≥ 30 without comorbidities was an AOM indication. Only 9.4% were correct on both of those indications for bariatric surgery.

“Reassuringly,” Campos said, the majority either “disagreed” or “strongly disagreed” that “lack of will power” contributes to obesity. However, more than 20% agreed that “lack of exercise or physical activity” contributed.

Overall, 73% of the trained providers and 59% of those in training reported that they prescribe AOMs. Asked about their comfort level in prescribing specific types of AOMs, many more endorsed semaglutide and liraglutide than older medications such as bupropion/naltrexone and phentermine/topiramate.

Asked about factors that influence their comfort with prescribing AOMs, the top five factors selected, in order, were side-effect knowledge, insurance coverage, safety issues, and dosing knowledge. Fewer respondents endorsed “patient’s ideas, concerns, and expectations,” cost, or efficacy.

Referrals to nutrition services were endorsed more often than to obesity medicine specialists or bariatric surgery.

Asked about barriers to obesity treatment in their practices, “time constraints” was the most frequently endorsed, followed by “lack of training or knowledge,” “patient adherence and motivation,” and “limited resources.”

“What are the future directives? We feel we have the need to provide ongoing obesity management, education and assistance to primary care providers, including support for securing coverage for treatments,” Campos said.

He added that Boston Medical Center is now developing and implementing an embedded weight management program within primary care “to assist the front line of obesity care.”

Asked by this news organization whether he believes the rise of GLP-1 drugs will make a difference, Campos said “Definitely, I think with that momentum obesity medicine as a whole will gain more attention and hopefully more implementation in the curricula for medical and nursing schools, because in the end it requires a multidisciplinary approach.”

Campos and Clark had no disclosures.

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

SAN ANTONIO — Despite the prevalence of obesity in primary care, there appear to be major knowledge gaps among providers regarding obesity management, new research suggests. 

Anonymous surveys of 96 primary care providers at a Boston, Massachusetts, safety-net hospital revealed that participants had limited understanding of criteria for prescribing antiobesity medications (AOM), and expressed discomfort in prescribing AOMs because of knowledge concerns, especially for non–glucagon-like peptide 1 (GLP-1) receptor agonists. One third reported that they didn’t prescribe AOMs, and rates of referral for bariatric surgery were also low. 

The findings were presented at the Obesity Society’s annual Obesity Week meeting by Alejandro Campos, MD, a third-year resident in the section of internal medicine, Boston Medical Center, and the Department of Medicine, Boston University. 

“I think it comes down to education. ... Not only training primary care physicians or residents about criteria and pathophysiology, but also stigma. Perceptions need to be addressed from the start of training in the healthcare field,” Campos told this news organization in an interview.

During his presentation, Campos noted this is the first such study in the setting of a safety-net hospital, which cares for lower-income people who experience disproportionate rates of obesity. But, “these findings are similar to ones observed from non–safety-net settings, which can indicate some potential transferability.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, told this news organization that the findings didn’t surprise him. “I’d say that medical education around obesity has definitely improved, and training is improving but it’s not uniform. The treatment of obesity as a disease, especially with some of the newer medical treatments, is not standard of care and practiced widely.”

The study involved a standard-model Knowledge, Attitudes, and Practices questionnaire, distributed electronically for anonymous responses among both trained and in-training primary care providers. It contained a total of 43 items, 7 of them demographic, 11 on knowledge, 9 regarding attitudes, and 16 asking about practices.

The hospital is the largest safety-net hospital in New England, with a patient population that includes 58% enrolled in Medicaid, 32% Black/African American individuals, 24% identifying as Hispanic/Latino individuals, and 37% living below the poverty line.

The 96 responding providers (from a total 350 invited) all worked in either family medicine or internal medicine. The trained providers included both attending MDs and nurse practitioners, while those in-training were residents in one of those two specialties. Two thirds were women. The majority were aged 20-30 years (49.45%) or 31-40 years (27.47%).

Overall, 73.63% reported having received some type of obesity training. Just over half (52.08%) reported receiving that training during medical or nursing school, while 43.75% reported receiving it during residency.

When asked to choose from a list of conditions to pick which are considered weight-related comorbidities, between 80% and 90% choose type 2 diabetes, obstructive sleep apnea (OSA), hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. Fewer, but still a majority, also listed osteoarthritis and gastroesophageal reflux disease. However, respondents were less likely to cite cancer, mood disorders, or chronic kidney disease as being related to obesity.

Asked to list benefits of a 10% body weight loss, most recognized reductions in OSA, glycemia, cardiovascular disease risk, osteoarthritis, and hepatic steatosis. But, only about half knew weight loss could also improve urinary incontinence.

Only 25% could correctly name both indications for AOMs. Just 27.1% knew that one was a body mass index (BMI) ≥ 27 with comorbidities, while 46.9% knew BMI ≥ 30 without comorbidities was an AOM indication. Only 9.4% were correct on both of those indications for bariatric surgery.

“Reassuringly,” Campos said, the majority either “disagreed” or “strongly disagreed” that “lack of will power” contributes to obesity. However, more than 20% agreed that “lack of exercise or physical activity” contributed.

Overall, 73% of the trained providers and 59% of those in training reported that they prescribe AOMs. Asked about their comfort level in prescribing specific types of AOMs, many more endorsed semaglutide and liraglutide than older medications such as bupropion/naltrexone and phentermine/topiramate.

Asked about factors that influence their comfort with prescribing AOMs, the top five factors selected, in order, were side-effect knowledge, insurance coverage, safety issues, and dosing knowledge. Fewer respondents endorsed “patient’s ideas, concerns, and expectations,” cost, or efficacy.

Referrals to nutrition services were endorsed more often than to obesity medicine specialists or bariatric surgery.

Asked about barriers to obesity treatment in their practices, “time constraints” was the most frequently endorsed, followed by “lack of training or knowledge,” “patient adherence and motivation,” and “limited resources.”

“What are the future directives? We feel we have the need to provide ongoing obesity management, education and assistance to primary care providers, including support for securing coverage for treatments,” Campos said.

He added that Boston Medical Center is now developing and implementing an embedded weight management program within primary care “to assist the front line of obesity care.”

Asked by this news organization whether he believes the rise of GLP-1 drugs will make a difference, Campos said “Definitely, I think with that momentum obesity medicine as a whole will gain more attention and hopefully more implementation in the curricula for medical and nursing schools, because in the end it requires a multidisciplinary approach.”

Campos and Clark had no disclosures.

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

SAN ANTONIO — Despite the prevalence of obesity in primary care, there appear to be major knowledge gaps among providers regarding obesity management, new research suggests. 

Anonymous surveys of 96 primary care providers at a Boston, Massachusetts, safety-net hospital revealed that participants had limited understanding of criteria for prescribing antiobesity medications (AOM), and expressed discomfort in prescribing AOMs because of knowledge concerns, especially for non–glucagon-like peptide 1 (GLP-1) receptor agonists. One third reported that they didn’t prescribe AOMs, and rates of referral for bariatric surgery were also low. 

The findings were presented at the Obesity Society’s annual Obesity Week meeting by Alejandro Campos, MD, a third-year resident in the section of internal medicine, Boston Medical Center, and the Department of Medicine, Boston University. 

“I think it comes down to education. ... Not only training primary care physicians or residents about criteria and pathophysiology, but also stigma. Perceptions need to be addressed from the start of training in the healthcare field,” Campos told this news organization in an interview.

During his presentation, Campos noted this is the first such study in the setting of a safety-net hospital, which cares for lower-income people who experience disproportionate rates of obesity. But, “these findings are similar to ones observed from non–safety-net settings, which can indicate some potential transferability.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, told this news organization that the findings didn’t surprise him. “I’d say that medical education around obesity has definitely improved, and training is improving but it’s not uniform. The treatment of obesity as a disease, especially with some of the newer medical treatments, is not standard of care and practiced widely.”

The study involved a standard-model Knowledge, Attitudes, and Practices questionnaire, distributed electronically for anonymous responses among both trained and in-training primary care providers. It contained a total of 43 items, 7 of them demographic, 11 on knowledge, 9 regarding attitudes, and 16 asking about practices.

The hospital is the largest safety-net hospital in New England, with a patient population that includes 58% enrolled in Medicaid, 32% Black/African American individuals, 24% identifying as Hispanic/Latino individuals, and 37% living below the poverty line.

The 96 responding providers (from a total 350 invited) all worked in either family medicine or internal medicine. The trained providers included both attending MDs and nurse practitioners, while those in-training were residents in one of those two specialties. Two thirds were women. The majority were aged 20-30 years (49.45%) or 31-40 years (27.47%).

Overall, 73.63% reported having received some type of obesity training. Just over half (52.08%) reported receiving that training during medical or nursing school, while 43.75% reported receiving it during residency.

When asked to choose from a list of conditions to pick which are considered weight-related comorbidities, between 80% and 90% choose type 2 diabetes, obstructive sleep apnea (OSA), hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. Fewer, but still a majority, also listed osteoarthritis and gastroesophageal reflux disease. However, respondents were less likely to cite cancer, mood disorders, or chronic kidney disease as being related to obesity.

Asked to list benefits of a 10% body weight loss, most recognized reductions in OSA, glycemia, cardiovascular disease risk, osteoarthritis, and hepatic steatosis. But, only about half knew weight loss could also improve urinary incontinence.

Only 25% could correctly name both indications for AOMs. Just 27.1% knew that one was a body mass index (BMI) ≥ 27 with comorbidities, while 46.9% knew BMI ≥ 30 without comorbidities was an AOM indication. Only 9.4% were correct on both of those indications for bariatric surgery.

“Reassuringly,” Campos said, the majority either “disagreed” or “strongly disagreed” that “lack of will power” contributes to obesity. However, more than 20% agreed that “lack of exercise or physical activity” contributed.

Overall, 73% of the trained providers and 59% of those in training reported that they prescribe AOMs. Asked about their comfort level in prescribing specific types of AOMs, many more endorsed semaglutide and liraglutide than older medications such as bupropion/naltrexone and phentermine/topiramate.

Asked about factors that influence their comfort with prescribing AOMs, the top five factors selected, in order, were side-effect knowledge, insurance coverage, safety issues, and dosing knowledge. Fewer respondents endorsed “patient’s ideas, concerns, and expectations,” cost, or efficacy.

Referrals to nutrition services were endorsed more often than to obesity medicine specialists or bariatric surgery.

Asked about barriers to obesity treatment in their practices, “time constraints” was the most frequently endorsed, followed by “lack of training or knowledge,” “patient adherence and motivation,” and “limited resources.”

“What are the future directives? We feel we have the need to provide ongoing obesity management, education and assistance to primary care providers, including support for securing coverage for treatments,” Campos said.

He added that Boston Medical Center is now developing and implementing an embedded weight management program within primary care “to assist the front line of obesity care.”

Asked by this news organization whether he believes the rise of GLP-1 drugs will make a difference, Campos said “Definitely, I think with that momentum obesity medicine as a whole will gain more attention and hopefully more implementation in the curricula for medical and nursing schools, because in the end it requires a multidisciplinary approach.”

Campos and Clark had no disclosures.

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

Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

For the past 4 years, primary care clinicians have labored under a seemingly endless onslaught of bad news. A recent report estimated that there were over 1.3 million excess deaths in the United States from March 2020 to May 2023, including nearly half a million Americans younger than age 65. Social isolation and an ailing economy accelerated preexisting rises in drug overdoses and obesity, while teenage vaping threatened to hook a new generation on tobacco products even as adult smoking plummeted. Meanwhile, more than half of the nation’s physicians now report feelings of burnout, pay for family doctors appears to be stagnating, and our interactions with an increasing number of patients are fraught with suspicions about the value of vaccines— not just against COVID-19 but against flu and other viruses, too — and the medical system as a whole, doctors included. 

Now, for the good news.

A year and a half since the end of the pandemic emergency, we are seeing gains on several fronts, and physicians deserve much of the credit. Preliminary data from the Centers for Disease Control and Prevention show that 10,000 fewer people died from drug overdoses than in the previous year. Although multiple factors contributed to this change, the elimination of the X-waiver, which had previously been required for physicians to prescribe buprenorphine for opioid use disorder, in January 2023 has improved access to medications for addiction treatment. In addition, the expansion of state requirements to check prescription drug monitoring programs when opioids or benzodiazepines are prescribed, and to prescribe naloxone to patients taking more than a certain number of morphine milligram equivalents per day, has probably reduced the harms of hazardous drug use.

On the obesity front, recent data from the National Health and Nutrition Examination Survey found that the prevalence of obesity in adults fell for the first time in more than a decade, from 41.9% to 40.3%. To be sure, obesity remains far too common, and this finding could be the result of statistical chance rather than representing a true decline. But the widespread prescribing of GLP-1 receptor agonists by primary care physicians, in particular, could have played a role in the encouraging trend.

Although more research is needed to prove causality, one analysis suggests that these drugs could easily have lowered the body mass index (BMI) of more than enough patients to account for the observed decline. What’s more, the rise in prevalence of BMIs above 40 (from 7.7% to 9.7%) could be explained by the mortality benefit of the drugs: More people remained in this severe obesity category because they didn’t die from complications of their weight. Whether future studies support keeping people on GLP-1s for life or eventually “off-ramping” them to other weight control strategies, family physicians are well positioned to help.

Finally, with little fanfare, the youth smoking rate has fallen precipitously. In 2023, 1.9% of high school students and 1.1% of middle-schoolers reported smoking cigarettes in the past 30 days. And they didn’t simply swap one form of nicotine delivery device for another. The 30-day prevalence of vaping among high school students fell from 27.5% in 2019 to 7.8% this year. Changing social norms and stricter federal regulation of tobacco products are probably more responsible for this positive trend than medical care, though the US Preventive Services Task Force recommends education or brief counseling to prevent initiation of tobacco use among school-aged children and adolescents. Should tobacco use in youth remain at these historically low levels, millions of premature deaths from lung cancer and heart disease will have been prevented.

America’s doctors have earned the right to take a bow. We have much more work to do, but our efforts are making a meaningful difference in three seemingly intractable health problems.

Dr. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

For the past 4 years, primary care clinicians have labored under a seemingly endless onslaught of bad news. A recent report estimated that there were over 1.3 million excess deaths in the United States from March 2020 to May 2023, including nearly half a million Americans younger than age 65. Social isolation and an ailing economy accelerated preexisting rises in drug overdoses and obesity, while teenage vaping threatened to hook a new generation on tobacco products even as adult smoking plummeted. Meanwhile, more than half of the nation’s physicians now report feelings of burnout, pay for family doctors appears to be stagnating, and our interactions with an increasing number of patients are fraught with suspicions about the value of vaccines— not just against COVID-19 but against flu and other viruses, too — and the medical system as a whole, doctors included. 

Now, for the good news.

A year and a half since the end of the pandemic emergency, we are seeing gains on several fronts, and physicians deserve much of the credit. Preliminary data from the Centers for Disease Control and Prevention show that 10,000 fewer people died from drug overdoses than in the previous year. Although multiple factors contributed to this change, the elimination of the X-waiver, which had previously been required for physicians to prescribe buprenorphine for opioid use disorder, in January 2023 has improved access to medications for addiction treatment. In addition, the expansion of state requirements to check prescription drug monitoring programs when opioids or benzodiazepines are prescribed, and to prescribe naloxone to patients taking more than a certain number of morphine milligram equivalents per day, has probably reduced the harms of hazardous drug use.

On the obesity front, recent data from the National Health and Nutrition Examination Survey found that the prevalence of obesity in adults fell for the first time in more than a decade, from 41.9% to 40.3%. To be sure, obesity remains far too common, and this finding could be the result of statistical chance rather than representing a true decline. But the widespread prescribing of GLP-1 receptor agonists by primary care physicians, in particular, could have played a role in the encouraging trend.

Although more research is needed to prove causality, one analysis suggests that these drugs could easily have lowered the body mass index (BMI) of more than enough patients to account for the observed decline. What’s more, the rise in prevalence of BMIs above 40 (from 7.7% to 9.7%) could be explained by the mortality benefit of the drugs: More people remained in this severe obesity category because they didn’t die from complications of their weight. Whether future studies support keeping people on GLP-1s for life or eventually “off-ramping” them to other weight control strategies, family physicians are well positioned to help.

Finally, with little fanfare, the youth smoking rate has fallen precipitously. In 2023, 1.9% of high school students and 1.1% of middle-schoolers reported smoking cigarettes in the past 30 days. And they didn’t simply swap one form of nicotine delivery device for another. The 30-day prevalence of vaping among high school students fell from 27.5% in 2019 to 7.8% this year. Changing social norms and stricter federal regulation of tobacco products are probably more responsible for this positive trend than medical care, though the US Preventive Services Task Force recommends education or brief counseling to prevent initiation of tobacco use among school-aged children and adolescents. Should tobacco use in youth remain at these historically low levels, millions of premature deaths from lung cancer and heart disease will have been prevented.

America’s doctors have earned the right to take a bow. We have much more work to do, but our efforts are making a meaningful difference in three seemingly intractable health problems.

Dr. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

For the past 4 years, primary care clinicians have labored under a seemingly endless onslaught of bad news. A recent report estimated that there were over 1.3 million excess deaths in the United States from March 2020 to May 2023, including nearly half a million Americans younger than age 65. Social isolation and an ailing economy accelerated preexisting rises in drug overdoses and obesity, while teenage vaping threatened to hook a new generation on tobacco products even as adult smoking plummeted. Meanwhile, more than half of the nation’s physicians now report feelings of burnout, pay for family doctors appears to be stagnating, and our interactions with an increasing number of patients are fraught with suspicions about the value of vaccines— not just against COVID-19 but against flu and other viruses, too — and the medical system as a whole, doctors included. 

Now, for the good news.

A year and a half since the end of the pandemic emergency, we are seeing gains on several fronts, and physicians deserve much of the credit. Preliminary data from the Centers for Disease Control and Prevention show that 10,000 fewer people died from drug overdoses than in the previous year. Although multiple factors contributed to this change, the elimination of the X-waiver, which had previously been required for physicians to prescribe buprenorphine for opioid use disorder, in January 2023 has improved access to medications for addiction treatment. In addition, the expansion of state requirements to check prescription drug monitoring programs when opioids or benzodiazepines are prescribed, and to prescribe naloxone to patients taking more than a certain number of morphine milligram equivalents per day, has probably reduced the harms of hazardous drug use.

On the obesity front, recent data from the National Health and Nutrition Examination Survey found that the prevalence of obesity in adults fell for the first time in more than a decade, from 41.9% to 40.3%. To be sure, obesity remains far too common, and this finding could be the result of statistical chance rather than representing a true decline. But the widespread prescribing of GLP-1 receptor agonists by primary care physicians, in particular, could have played a role in the encouraging trend.

Although more research is needed to prove causality, one analysis suggests that these drugs could easily have lowered the body mass index (BMI) of more than enough patients to account for the observed decline. What’s more, the rise in prevalence of BMIs above 40 (from 7.7% to 9.7%) could be explained by the mortality benefit of the drugs: More people remained in this severe obesity category because they didn’t die from complications of their weight. Whether future studies support keeping people on GLP-1s for life or eventually “off-ramping” them to other weight control strategies, family physicians are well positioned to help.

Finally, with little fanfare, the youth smoking rate has fallen precipitously. In 2023, 1.9% of high school students and 1.1% of middle-schoolers reported smoking cigarettes in the past 30 days. And they didn’t simply swap one form of nicotine delivery device for another. The 30-day prevalence of vaping among high school students fell from 27.5% in 2019 to 7.8% this year. Changing social norms and stricter federal regulation of tobacco products are probably more responsible for this positive trend than medical care, though the US Preventive Services Task Force recommends education or brief counseling to prevent initiation of tobacco use among school-aged children and adolescents. Should tobacco use in youth remain at these historically low levels, millions of premature deaths from lung cancer and heart disease will have been prevented.

America’s doctors have earned the right to take a bow. We have much more work to do, but our efforts are making a meaningful difference in three seemingly intractable health problems.

Dr. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

TOPLINE:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

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:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

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:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

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:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. 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 first appeared on Medscape.com.

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. 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 first appeared on Medscape.com.

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. 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 first appeared on Medscape.com.

SAN ANTONIO, TEXAS — An upcoming document will entirely reframe obesity as a “condition of excess adiposity” that constitutes a disease called “clinical obesity” when related tissue and organ abnormalities are present.

The authors of the new framework are a Lancet Commission of 56 of the world’s leading obesity experts, including academic clinicians, scientists, public health experts, patient representatives, and officers from the World Health Organization. Following peer review, it will be launched via livestream and published in Lancet Diabetes & Endocrinology in mid-January 2025, with formal endorsement from more than 75 medical societies and other relevant stakeholder organizations.

On November 4, 2024, at the Obesity Society’s Obesity Week meeting, the publication’s lead author, Francesco Rubino, MD, Chair of Bariatric and Metabolic Surgery at King’s College London in England, gave a preview. He began by noting that, despite the declaration of obesity as a chronic disease over a decade ago, the concept is still debated and not widely accepted by the public or even by all in the medical community.

“The idea of obesity as a disease remains highly controversial,” Rubino noted, adding that the current body mass index (BMI)–based definition contributes to this because it doesn’t distinguish between people whose excess adiposity place them at excess risk for disease but they’re currently healthy vs those who already have undergone bodily harm from that adiposity.

“Having a framework that distinguishes at an individual level when you are in a condition of risk and when you have a condition of disease is fundamentally important. You don’t want to blur the picture in either direction, because obviously the consequence would be quite significant. ... So, the commission focused exactly on that point,” he said.

The new paper will propose a two-part clinical approach: First, assess whether the patient has excess adiposity, with methods that will be outlined. Next, assess on an organ-by-organ basis for the presence of abnormalities related to excess adiposity, or “clinical obesity.” The document will also provide those specific criteria, Rubino said, noting that those details are under embargo until January.

However, he did say that “We are going to propose a pragmatic approach to say that BMI alone is not enough in the clinic. It’s okay as a screening tool, but when somebody potentially has obesity, then you have to add additional measures of adiposity that makes sure you decrease the level of risk… Once you have obesity, then you need to establish if it’s clinical or nonclinical.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, said in an interview, “I think it’ll help explain and move medicine as a whole in a direction to a greater understanding of obesity actually being a disease, how to define it, and how to identify it. And will, I think, lead to a greater understanding of the underlying disease.”

And, Clark said, it should also help target individuals with preventive vs therapeutic approaches. “I would describe it as matching the right tool to the right patient. If a person has clinical obesity, they likely can and would benefit from either different or additional tools, as opposed to otherwise healthy obesity.”

Rubino said he hopes the new framework will prompt improvements in reimbursement and public policy. “Policymakers scratch their heads when they have limited resources and you need to prioritize things. Having an obesity definition that is blurry doesn’t allow you to have a fair, human, and meaningful prioritization. ... Now that we have drugs that cannot be given to 100% of people, how do you decide who gets them first? I hope this will make it easier for people to access treatment. At the moment, it is not only difficult, but it’s also unfair. It’s random. Somebody gets access, while somebody else who is very, very sick has no access. I don’t think that’s what we want.”

A version of this article appeared on Medscape.com.

SAN ANTONIO, TEXAS — An upcoming document will entirely reframe obesity as a “condition of excess adiposity” that constitutes a disease called “clinical obesity” when related tissue and organ abnormalities are present.

The authors of the new framework are a Lancet Commission of 56 of the world’s leading obesity experts, including academic clinicians, scientists, public health experts, patient representatives, and officers from the World Health Organization. Following peer review, it will be launched via livestream and published in Lancet Diabetes & Endocrinology in mid-January 2025, with formal endorsement from more than 75 medical societies and other relevant stakeholder organizations.

On November 4, 2024, at the Obesity Society’s Obesity Week meeting, the publication’s lead author, Francesco Rubino, MD, Chair of Bariatric and Metabolic Surgery at King’s College London in England, gave a preview. He began by noting that, despite the declaration of obesity as a chronic disease over a decade ago, the concept is still debated and not widely accepted by the public or even by all in the medical community.

“The idea of obesity as a disease remains highly controversial,” Rubino noted, adding that the current body mass index (BMI)–based definition contributes to this because it doesn’t distinguish between people whose excess adiposity place them at excess risk for disease but they’re currently healthy vs those who already have undergone bodily harm from that adiposity.

“Having a framework that distinguishes at an individual level when you are in a condition of risk and when you have a condition of disease is fundamentally important. You don’t want to blur the picture in either direction, because obviously the consequence would be quite significant. ... So, the commission focused exactly on that point,” he said.

The new paper will propose a two-part clinical approach: First, assess whether the patient has excess adiposity, with methods that will be outlined. Next, assess on an organ-by-organ basis for the presence of abnormalities related to excess adiposity, or “clinical obesity.” The document will also provide those specific criteria, Rubino said, noting that those details are under embargo until January.

However, he did say that “We are going to propose a pragmatic approach to say that BMI alone is not enough in the clinic. It’s okay as a screening tool, but when somebody potentially has obesity, then you have to add additional measures of adiposity that makes sure you decrease the level of risk… Once you have obesity, then you need to establish if it’s clinical or nonclinical.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, said in an interview, “I think it’ll help explain and move medicine as a whole in a direction to a greater understanding of obesity actually being a disease, how to define it, and how to identify it. And will, I think, lead to a greater understanding of the underlying disease.”

And, Clark said, it should also help target individuals with preventive vs therapeutic approaches. “I would describe it as matching the right tool to the right patient. If a person has clinical obesity, they likely can and would benefit from either different or additional tools, as opposed to otherwise healthy obesity.”

Rubino said he hopes the new framework will prompt improvements in reimbursement and public policy. “Policymakers scratch their heads when they have limited resources and you need to prioritize things. Having an obesity definition that is blurry doesn’t allow you to have a fair, human, and meaningful prioritization. ... Now that we have drugs that cannot be given to 100% of people, how do you decide who gets them first? I hope this will make it easier for people to access treatment. At the moment, it is not only difficult, but it’s also unfair. It’s random. Somebody gets access, while somebody else who is very, very sick has no access. I don’t think that’s what we want.”

A version of this article appeared on Medscape.com.

SAN ANTONIO, TEXAS — An upcoming document will entirely reframe obesity as a “condition of excess adiposity” that constitutes a disease called “clinical obesity” when related tissue and organ abnormalities are present.

The authors of the new framework are a Lancet Commission of 56 of the world’s leading obesity experts, including academic clinicians, scientists, public health experts, patient representatives, and officers from the World Health Organization. Following peer review, it will be launched via livestream and published in Lancet Diabetes & Endocrinology in mid-January 2025, with formal endorsement from more than 75 medical societies and other relevant stakeholder organizations.

On November 4, 2024, at the Obesity Society’s Obesity Week meeting, the publication’s lead author, Francesco Rubino, MD, Chair of Bariatric and Metabolic Surgery at King’s College London in England, gave a preview. He began by noting that, despite the declaration of obesity as a chronic disease over a decade ago, the concept is still debated and not widely accepted by the public or even by all in the medical community.

“The idea of obesity as a disease remains highly controversial,” Rubino noted, adding that the current body mass index (BMI)–based definition contributes to this because it doesn’t distinguish between people whose excess adiposity place them at excess risk for disease but they’re currently healthy vs those who already have undergone bodily harm from that adiposity.

“Having a framework that distinguishes at an individual level when you are in a condition of risk and when you have a condition of disease is fundamentally important. You don’t want to blur the picture in either direction, because obviously the consequence would be quite significant. ... So, the commission focused exactly on that point,” he said.

The new paper will propose a two-part clinical approach: First, assess whether the patient has excess adiposity, with methods that will be outlined. Next, assess on an organ-by-organ basis for the presence of abnormalities related to excess adiposity, or “clinical obesity.” The document will also provide those specific criteria, Rubino said, noting that those details are under embargo until January.

However, he did say that “We are going to propose a pragmatic approach to say that BMI alone is not enough in the clinic. It’s okay as a screening tool, but when somebody potentially has obesity, then you have to add additional measures of adiposity that makes sure you decrease the level of risk… Once you have obesity, then you need to establish if it’s clinical or nonclinical.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, said in an interview, “I think it’ll help explain and move medicine as a whole in a direction to a greater understanding of obesity actually being a disease, how to define it, and how to identify it. And will, I think, lead to a greater understanding of the underlying disease.”

And, Clark said, it should also help target individuals with preventive vs therapeutic approaches. “I would describe it as matching the right tool to the right patient. If a person has clinical obesity, they likely can and would benefit from either different or additional tools, as opposed to otherwise healthy obesity.”

Rubino said he hopes the new framework will prompt improvements in reimbursement and public policy. “Policymakers scratch their heads when they have limited resources and you need to prioritize things. Having an obesity definition that is blurry doesn’t allow you to have a fair, human, and meaningful prioritization. ... Now that we have drugs that cannot be given to 100% of people, how do you decide who gets them first? I hope this will make it easier for people to access treatment. At the moment, it is not only difficult, but it’s also unfair. It’s random. Somebody gets access, while somebody else who is very, very sick has no access. I don’t think that’s what we want.”

A version of this article appeared on Medscape.com.

Metabolic dysfunction–associated steatotic liver disease (MASLD) has become the most common liver disease worldwide, with a global prevalence of 32.4%. Its growth over the past three decades has occurred in tandem with increasing rates of obesity and type 2 diabetes — two cornerstones of MASLD.

Higher rates of MASLD and metabolic dysfunction–associated steatohepatitis (MASH) with fibrosis are present in adults with obesity and diabetes, noted Arun Sanyal, MD, professor and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia.

The success surrounding the medications for obesity and type 2 diabetes, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs), has sparked studies investigating whether they could also be an effective treatment for liver disease.

In particular, GLP-1 RAs help patients lose weight and/or control diabetes by mimicking the function of the gut hormone GLP-1, released in response to nutrient intake, and are able to increase insulin secretion and reduce glucagon secretion, delay gastric emptying, and reduce appetite and caloric intake.

The studies for MASLD are testing whether these functions will also work against liver disease, either directly or indirectly, through obesity and diabetes control. The early results are promising.
 

More Than One Risk Factor in Play

MASLD is defined by the presence of hepatic steatosis and at least one of five cardiometabolic risk factors: Overweight/obesity, hypertension, hyperglycemia, dyslipidemia with either low-plasma high-density lipoprotein cholesterol or high triglycerides, or treatment for these conditions.

It is a grim trajectory if the disease progresses to MASH, as the patient may accumulate hepatic fibrosis and go on to develop cirrhosis and/or hepatocellular carcinoma.

Typically, more than one risk factor is at play in MASLD, noted Adnan Said, MD, chief of the Division of Gastroenterology and Hepatology at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.

“It most commonly occurs in the setting of weight gain and obesity, which are epidemics in the United States and worldwide, as well as the associated condition — metabolic syndrome — which goes along with obesity and includes type 2 diabetes, hyperlipidemia, hypertension, and sleep apnea,” Said, a hepatology and gastroenterology professor at the University of Wisconsin–Madison, told this news organization.

The research surrounding MASLD is investigating GLP-1 RAs as single agents and in combination with other drugs.

Finding treatment is critical, as there is only one drug — resmetirom — approved for the treatment of MASH with moderate to advanced fibrosis. But because it’s not approved for earlier stages, a treatment gap exists. The drug also doesn’t produce weight loss, which is key to treating MASLD. And while GLP-1 RAs help patients with the weight loss that is critical to MASLD, they are only approved by the US Food and Drug Administration (FDA) for obesity and type 2 diabetes.
 

Single Agents

The GLP-1 RAs liraglutide and semaglutide, both approved for diabetes and weight loss, are being studied as single agents against liver disease, Said said.

“Their action in the setting of MASLD and MASH is primarily indirect, through systemic pathways, improving these conditions via weight loss, as well as by improving insulin sensitivity and reducing lipotoxicity,” he added.

One of the first trials of these agents for liver disease was in 2016. In that double-blind, randomized, 48-week clinical trial of liraglutide in patients with MASH and overweight, 39% of patients who received liraglutide had a resolution of MASH compared with only 9% of those who received placebo. Moreover, only 9% vs 36% of patients in the treatment vs placebo group had progression of fibrosis.

Since then, a 72-week phase 2 trial in patients with MASH, liver fibrosis (stages F1-F3), and overweight or obesity found that once-daily subcutaneous semaglutide (0.1, 0.2, or 0.4 mg) outperformed placebo on MASH resolution without worsening of fibrosis (36%-59% vs 17%) and on weight loss (5%-13% vs 1%), with the greatest benefits at the largest dose. However, neoplasms were reported in 15% of patients receiving semaglutide vs 8% of those receiving placebo.

A phase 1 trial involving patients with liver stiffness, steatosis, and overweight or obesity found significantly greater reductions in liver fat at 48 weeks with semaglutide vs placebo, as well as decreases in liver enzymes, body weight, and A1c. There was no significant difference in liver stiffness.

Furthermore, a meta-analysis of eight studies found that treatment with 24 weeks of semaglutide significantly improved liver enzymes, reduced liver stiffness, and improved metabolic parameters in patients with MASLD/MASH. The authors cautioned that gastrointestinal adverse effects “could be a major concern.”

Several studies have found other GLP-1 RAs, including exenatide and dulaglutide, have a beneficial impact on liver injury indices and liver steatosis.

A new retrospective observational study offers evidence that GLP-1 RAs may have a direct impact on MASLD, independent of weight loss. Among the 28% of patients with type 2 diabetes and MASLD who received a GLP-1 RA, there was a significant reduction not only in body mass index but also in A1c, liver enzymes, and controlled attenuation parameter scores. A beneficial impact on liver parameters was observed even in patients who didn’t lose weight. While there was no difference in liver stiffness measurement, the median 60-month follow-up time may not have been long enough to capture such changes.

Another study indicated that the apparent benefits of GLP-1 RAs, in this case semaglutide, may not extend to patients whose disease has progressed to cirrhosis.
 

Dual and Triple Mechanisms of Action

Newer agents with double or triple mechanisms of action appear to have a more direct effect on the liver.

“Dual agents may have an added effect by improving MASLD directly through adipose regulation and thermogenesis, thereby improving fibrosis,” Said said.

An example is tirzepatide, a GLP-1 RA and an agonist of glucose-dependent insulinotropic polypeptide (GIP). Like GLP-1, GIP is an incretin. When used together as co-agonists, GLP-1 and GIP have been shown to increase insulin and glucagonostatic response and may work synergistically.

A new phase 2 trial that randomly assigned patients with biopsy-confirmed MASH and moderate or severe fibrosis to receive either once-weekly subcutaneous tirzepatide at one of three doses (5, 10, or 15 mg) or placebo found that tirzepatide at each dosage outperformed placebo in resolution of MASH without worsening of fibrosis.

“These findings were encouraging,” Said said. “We’ll see if the results continue into phase 3 trials.”

The combination of GLP-1 RAs with glucagon (GCG) receptor agonists also has garnered interest.

In a phase 2 trial, adults with biopsy-confirmed MASH and fibrosis stages F1-F3 were randomly assigned to receive either one of three doses of the GLP-1/GCG RA survodutide (2.4, 4.8, or 6 mg) or placebo. Survodutide at each dose was found to be superior to placebo in improving MASH without the worsening of fibrosis, reducing liver fat content by at least 30%, and decreasing liver fibrosis by at least one stage, with the 4.8-mg dose showing the best performance for each measure. However, adverse events, including nausea, diarrhea, and vomiting, were more frequent with survodutide than with placebo.

Trials of triple-action agents (GLP-1/GIP/GCG RAs) are underway too.

The hope is the triple agonists could deliver greater reduction in hepatic fat in patients with MASLD, Sanyal said. 

Sanyal further noted that a reduction in liver fat is important, citing a meta-analysis that showed ≥ 30% relative decline in liver fat is associated with higher odds of histologic response and MASH resolution.

Sanyal pointed to efocipegtrutide (HM15211), a GLP-1/GIP/GCG RA, which demonstrated significant liver fat reduction after 12 weeks in patients with MASLD in a phase 1b/2a randomized, placebo-controlled trial and is now in phase 2 development.

Another example is retatrutide (LY3437943), a once-weekly injectable, that was associated with up to a 24.2% reduction in body weight at 48 weeks, compared with 2.1% with placebo, in a phase 2 trial involving patients with obesity.

A sub-study assessed the mean relative change from baseline in liver fat at 24 weeks. These participants, who also had MASLD and ≥ 10% of liver fat content, were randomly assigned to receive either retatrutide in one of four doses (1, 4, 8, or 12 mg) or placebo for 48 weeks. All doses of retatrutide showed significantly greater reduction in liver fat content compared with placebo in weeks 24-48, with a mean relative liver fat reduction > 80% at the two higher doses. Moreover, ≥ 80% of participants on the higher retatrutide doses experienced ≥ 70% reduction in liver fat at 48 weeks, compared with 0% reduction in those on placebo, and hepatic steatosis resolved in > 85% of these participants.

This space “continues to evolve at a rapid rate,” Sanyal said. For example, oral dual-action agents are under development.
 

Obstacles and Warnings

Sanyal warned that GLP-1 RAs can cause nausea, so they have to be introduced at a low dose and slowly titrated upward. They should be used with caution in people with a history of multiple endocrine neoplasia. There is also a small but increased risk for gallstone formation and gallstone-induced pancreatitis with rapid weight loss.

GLP-1 RAs may increase the risk for suicidal ideation, with the authors of a recent study calling for “urgent clarification” regarding this possibility.

Following reports of suicidality submitted through its Adverse Events Reporting System, the FDA concluded that it could find no causal relationship between these agents and increased risk for suicidal ideation but also that it could not “definitively rule out that a small risk may exist” and would continue to investigate.

Access to GLP-1 RAs is an obstacle as well. Semaglutide continues to be on the FDA’s shortage list.

“This is improving, but there are still issues around getting approval from insurance companies,” Sanyal said.

Many patients discontinue use because of tolerability or access issues, which is problematic because most regain the weight they had lost while on the medication.

“Right now, we see GLP-1 RAs as a long-term therapeutic commitment, but there is a lot of research interest in figuring out if there’s a more modest benefit — almost an induction-remission maintenance approach to weight loss,” Sanyal said. These are “evolving trends,” and it’s unclear how they will unfold.

“As of now, you have to decide that if you’re putting your patient on these medications, they will have to take them on a long-term basis and include that consideration in your risk-benefit analysis, together with any concerns about adverse effects,” he said.

Sanyal reported consulting for Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Said received research support from Exact Sciences, Boehringer Ingelheim, and Mallinckrodt.
 

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

Metabolic dysfunction–associated steatotic liver disease (MASLD) has become the most common liver disease worldwide, with a global prevalence of 32.4%. Its growth over the past three decades has occurred in tandem with increasing rates of obesity and type 2 diabetes — two cornerstones of MASLD.

Higher rates of MASLD and metabolic dysfunction–associated steatohepatitis (MASH) with fibrosis are present in adults with obesity and diabetes, noted Arun Sanyal, MD, professor and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia.

The success surrounding the medications for obesity and type 2 diabetes, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs), has sparked studies investigating whether they could also be an effective treatment for liver disease.

In particular, GLP-1 RAs help patients lose weight and/or control diabetes by mimicking the function of the gut hormone GLP-1, released in response to nutrient intake, and are able to increase insulin secretion and reduce glucagon secretion, delay gastric emptying, and reduce appetite and caloric intake.

The studies for MASLD are testing whether these functions will also work against liver disease, either directly or indirectly, through obesity and diabetes control. The early results are promising.
 

More Than One Risk Factor in Play

MASLD is defined by the presence of hepatic steatosis and at least one of five cardiometabolic risk factors: Overweight/obesity, hypertension, hyperglycemia, dyslipidemia with either low-plasma high-density lipoprotein cholesterol or high triglycerides, or treatment for these conditions.

It is a grim trajectory if the disease progresses to MASH, as the patient may accumulate hepatic fibrosis and go on to develop cirrhosis and/or hepatocellular carcinoma.

Typically, more than one risk factor is at play in MASLD, noted Adnan Said, MD, chief of the Division of Gastroenterology and Hepatology at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.

“It most commonly occurs in the setting of weight gain and obesity, which are epidemics in the United States and worldwide, as well as the associated condition — metabolic syndrome — which goes along with obesity and includes type 2 diabetes, hyperlipidemia, hypertension, and sleep apnea,” Said, a hepatology and gastroenterology professor at the University of Wisconsin–Madison, told this news organization.

The research surrounding MASLD is investigating GLP-1 RAs as single agents and in combination with other drugs.

Finding treatment is critical, as there is only one drug — resmetirom — approved for the treatment of MASH with moderate to advanced fibrosis. But because it’s not approved for earlier stages, a treatment gap exists. The drug also doesn’t produce weight loss, which is key to treating MASLD. And while GLP-1 RAs help patients with the weight loss that is critical to MASLD, they are only approved by the US Food and Drug Administration (FDA) for obesity and type 2 diabetes.
 

Single Agents

The GLP-1 RAs liraglutide and semaglutide, both approved for diabetes and weight loss, are being studied as single agents against liver disease, Said said.

“Their action in the setting of MASLD and MASH is primarily indirect, through systemic pathways, improving these conditions via weight loss, as well as by improving insulin sensitivity and reducing lipotoxicity,” he added.

One of the first trials of these agents for liver disease was in 2016. In that double-blind, randomized, 48-week clinical trial of liraglutide in patients with MASH and overweight, 39% of patients who received liraglutide had a resolution of MASH compared with only 9% of those who received placebo. Moreover, only 9% vs 36% of patients in the treatment vs placebo group had progression of fibrosis.

Since then, a 72-week phase 2 trial in patients with MASH, liver fibrosis (stages F1-F3), and overweight or obesity found that once-daily subcutaneous semaglutide (0.1, 0.2, or 0.4 mg) outperformed placebo on MASH resolution without worsening of fibrosis (36%-59% vs 17%) and on weight loss (5%-13% vs 1%), with the greatest benefits at the largest dose. However, neoplasms were reported in 15% of patients receiving semaglutide vs 8% of those receiving placebo.

A phase 1 trial involving patients with liver stiffness, steatosis, and overweight or obesity found significantly greater reductions in liver fat at 48 weeks with semaglutide vs placebo, as well as decreases in liver enzymes, body weight, and A1c. There was no significant difference in liver stiffness.

Furthermore, a meta-analysis of eight studies found that treatment with 24 weeks of semaglutide significantly improved liver enzymes, reduced liver stiffness, and improved metabolic parameters in patients with MASLD/MASH. The authors cautioned that gastrointestinal adverse effects “could be a major concern.”

Several studies have found other GLP-1 RAs, including exenatide and dulaglutide, have a beneficial impact on liver injury indices and liver steatosis.

A new retrospective observational study offers evidence that GLP-1 RAs may have a direct impact on MASLD, independent of weight loss. Among the 28% of patients with type 2 diabetes and MASLD who received a GLP-1 RA, there was a significant reduction not only in body mass index but also in A1c, liver enzymes, and controlled attenuation parameter scores. A beneficial impact on liver parameters was observed even in patients who didn’t lose weight. While there was no difference in liver stiffness measurement, the median 60-month follow-up time may not have been long enough to capture such changes.

Another study indicated that the apparent benefits of GLP-1 RAs, in this case semaglutide, may not extend to patients whose disease has progressed to cirrhosis.
 

Dual and Triple Mechanisms of Action

Newer agents with double or triple mechanisms of action appear to have a more direct effect on the liver.

“Dual agents may have an added effect by improving MASLD directly through adipose regulation and thermogenesis, thereby improving fibrosis,” Said said.

An example is tirzepatide, a GLP-1 RA and an agonist of glucose-dependent insulinotropic polypeptide (GIP). Like GLP-1, GIP is an incretin. When used together as co-agonists, GLP-1 and GIP have been shown to increase insulin and glucagonostatic response and may work synergistically.

A new phase 2 trial that randomly assigned patients with biopsy-confirmed MASH and moderate or severe fibrosis to receive either once-weekly subcutaneous tirzepatide at one of three doses (5, 10, or 15 mg) or placebo found that tirzepatide at each dosage outperformed placebo in resolution of MASH without worsening of fibrosis.

“These findings were encouraging,” Said said. “We’ll see if the results continue into phase 3 trials.”

The combination of GLP-1 RAs with glucagon (GCG) receptor agonists also has garnered interest.

In a phase 2 trial, adults with biopsy-confirmed MASH and fibrosis stages F1-F3 were randomly assigned to receive either one of three doses of the GLP-1/GCG RA survodutide (2.4, 4.8, or 6 mg) or placebo. Survodutide at each dose was found to be superior to placebo in improving MASH without the worsening of fibrosis, reducing liver fat content by at least 30%, and decreasing liver fibrosis by at least one stage, with the 4.8-mg dose showing the best performance for each measure. However, adverse events, including nausea, diarrhea, and vomiting, were more frequent with survodutide than with placebo.

Trials of triple-action agents (GLP-1/GIP/GCG RAs) are underway too.

The hope is the triple agonists could deliver greater reduction in hepatic fat in patients with MASLD, Sanyal said. 

Sanyal further noted that a reduction in liver fat is important, citing a meta-analysis that showed ≥ 30% relative decline in liver fat is associated with higher odds of histologic response and MASH resolution.

Sanyal pointed to efocipegtrutide (HM15211), a GLP-1/GIP/GCG RA, which demonstrated significant liver fat reduction after 12 weeks in patients with MASLD in a phase 1b/2a randomized, placebo-controlled trial and is now in phase 2 development.

Another example is retatrutide (LY3437943), a once-weekly injectable, that was associated with up to a 24.2% reduction in body weight at 48 weeks, compared with 2.1% with placebo, in a phase 2 trial involving patients with obesity.

A sub-study assessed the mean relative change from baseline in liver fat at 24 weeks. These participants, who also had MASLD and ≥ 10% of liver fat content, were randomly assigned to receive either retatrutide in one of four doses (1, 4, 8, or 12 mg) or placebo for 48 weeks. All doses of retatrutide showed significantly greater reduction in liver fat content compared with placebo in weeks 24-48, with a mean relative liver fat reduction > 80% at the two higher doses. Moreover, ≥ 80% of participants on the higher retatrutide doses experienced ≥ 70% reduction in liver fat at 48 weeks, compared with 0% reduction in those on placebo, and hepatic steatosis resolved in > 85% of these participants.

This space “continues to evolve at a rapid rate,” Sanyal said. For example, oral dual-action agents are under development.
 

Obstacles and Warnings

Sanyal warned that GLP-1 RAs can cause nausea, so they have to be introduced at a low dose and slowly titrated upward. They should be used with caution in people with a history of multiple endocrine neoplasia. There is also a small but increased risk for gallstone formation and gallstone-induced pancreatitis with rapid weight loss.

GLP-1 RAs may increase the risk for suicidal ideation, with the authors of a recent study calling for “urgent clarification” regarding this possibility.

Following reports of suicidality submitted through its Adverse Events Reporting System, the FDA concluded that it could find no causal relationship between these agents and increased risk for suicidal ideation but also that it could not “definitively rule out that a small risk may exist” and would continue to investigate.

Access to GLP-1 RAs is an obstacle as well. Semaglutide continues to be on the FDA’s shortage list.

“This is improving, but there are still issues around getting approval from insurance companies,” Sanyal said.

Many patients discontinue use because of tolerability or access issues, which is problematic because most regain the weight they had lost while on the medication.

“Right now, we see GLP-1 RAs as a long-term therapeutic commitment, but there is a lot of research interest in figuring out if there’s a more modest benefit — almost an induction-remission maintenance approach to weight loss,” Sanyal said. These are “evolving trends,” and it’s unclear how they will unfold.

“As of now, you have to decide that if you’re putting your patient on these medications, they will have to take them on a long-term basis and include that consideration in your risk-benefit analysis, together with any concerns about adverse effects,” he said.

Sanyal reported consulting for Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Said received research support from Exact Sciences, Boehringer Ingelheim, and Mallinckrodt.
 

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

Metabolic dysfunction–associated steatotic liver disease (MASLD) has become the most common liver disease worldwide, with a global prevalence of 32.4%. Its growth over the past three decades has occurred in tandem with increasing rates of obesity and type 2 diabetes — two cornerstones of MASLD.

Higher rates of MASLD and metabolic dysfunction–associated steatohepatitis (MASH) with fibrosis are present in adults with obesity and diabetes, noted Arun Sanyal, MD, professor and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia.

The success surrounding the medications for obesity and type 2 diabetes, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs), has sparked studies investigating whether they could also be an effective treatment for liver disease.

In particular, GLP-1 RAs help patients lose weight and/or control diabetes by mimicking the function of the gut hormone GLP-1, released in response to nutrient intake, and are able to increase insulin secretion and reduce glucagon secretion, delay gastric emptying, and reduce appetite and caloric intake.

The studies for MASLD are testing whether these functions will also work against liver disease, either directly or indirectly, through obesity and diabetes control. The early results are promising.
 

More Than One Risk Factor in Play

MASLD is defined by the presence of hepatic steatosis and at least one of five cardiometabolic risk factors: Overweight/obesity, hypertension, hyperglycemia, dyslipidemia with either low-plasma high-density lipoprotein cholesterol or high triglycerides, or treatment for these conditions.

It is a grim trajectory if the disease progresses to MASH, as the patient may accumulate hepatic fibrosis and go on to develop cirrhosis and/or hepatocellular carcinoma.

Typically, more than one risk factor is at play in MASLD, noted Adnan Said, MD, chief of the Division of Gastroenterology and Hepatology at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.

“It most commonly occurs in the setting of weight gain and obesity, which are epidemics in the United States and worldwide, as well as the associated condition — metabolic syndrome — which goes along with obesity and includes type 2 diabetes, hyperlipidemia, hypertension, and sleep apnea,” Said, a hepatology and gastroenterology professor at the University of Wisconsin–Madison, told this news organization.

The research surrounding MASLD is investigating GLP-1 RAs as single agents and in combination with other drugs.

Finding treatment is critical, as there is only one drug — resmetirom — approved for the treatment of MASH with moderate to advanced fibrosis. But because it’s not approved for earlier stages, a treatment gap exists. The drug also doesn’t produce weight loss, which is key to treating MASLD. And while GLP-1 RAs help patients with the weight loss that is critical to MASLD, they are only approved by the US Food and Drug Administration (FDA) for obesity and type 2 diabetes.
 

Single Agents

The GLP-1 RAs liraglutide and semaglutide, both approved for diabetes and weight loss, are being studied as single agents against liver disease, Said said.

“Their action in the setting of MASLD and MASH is primarily indirect, through systemic pathways, improving these conditions via weight loss, as well as by improving insulin sensitivity and reducing lipotoxicity,” he added.

One of the first trials of these agents for liver disease was in 2016. In that double-blind, randomized, 48-week clinical trial of liraglutide in patients with MASH and overweight, 39% of patients who received liraglutide had a resolution of MASH compared with only 9% of those who received placebo. Moreover, only 9% vs 36% of patients in the treatment vs placebo group had progression of fibrosis.

Since then, a 72-week phase 2 trial in patients with MASH, liver fibrosis (stages F1-F3), and overweight or obesity found that once-daily subcutaneous semaglutide (0.1, 0.2, or 0.4 mg) outperformed placebo on MASH resolution without worsening of fibrosis (36%-59% vs 17%) and on weight loss (5%-13% vs 1%), with the greatest benefits at the largest dose. However, neoplasms were reported in 15% of patients receiving semaglutide vs 8% of those receiving placebo.

A phase 1 trial involving patients with liver stiffness, steatosis, and overweight or obesity found significantly greater reductions in liver fat at 48 weeks with semaglutide vs placebo, as well as decreases in liver enzymes, body weight, and A1c. There was no significant difference in liver stiffness.

Furthermore, a meta-analysis of eight studies found that treatment with 24 weeks of semaglutide significantly improved liver enzymes, reduced liver stiffness, and improved metabolic parameters in patients with MASLD/MASH. The authors cautioned that gastrointestinal adverse effects “could be a major concern.”

Several studies have found other GLP-1 RAs, including exenatide and dulaglutide, have a beneficial impact on liver injury indices and liver steatosis.

A new retrospective observational study offers evidence that GLP-1 RAs may have a direct impact on MASLD, independent of weight loss. Among the 28% of patients with type 2 diabetes and MASLD who received a GLP-1 RA, there was a significant reduction not only in body mass index but also in A1c, liver enzymes, and controlled attenuation parameter scores. A beneficial impact on liver parameters was observed even in patients who didn’t lose weight. While there was no difference in liver stiffness measurement, the median 60-month follow-up time may not have been long enough to capture such changes.

Another study indicated that the apparent benefits of GLP-1 RAs, in this case semaglutide, may not extend to patients whose disease has progressed to cirrhosis.
 

Dual and Triple Mechanisms of Action

Newer agents with double or triple mechanisms of action appear to have a more direct effect on the liver.

“Dual agents may have an added effect by improving MASLD directly through adipose regulation and thermogenesis, thereby improving fibrosis,” Said said.

An example is tirzepatide, a GLP-1 RA and an agonist of glucose-dependent insulinotropic polypeptide (GIP). Like GLP-1, GIP is an incretin. When used together as co-agonists, GLP-1 and GIP have been shown to increase insulin and glucagonostatic response and may work synergistically.

A new phase 2 trial that randomly assigned patients with biopsy-confirmed MASH and moderate or severe fibrosis to receive either once-weekly subcutaneous tirzepatide at one of three doses (5, 10, or 15 mg) or placebo found that tirzepatide at each dosage outperformed placebo in resolution of MASH without worsening of fibrosis.

“These findings were encouraging,” Said said. “We’ll see if the results continue into phase 3 trials.”

The combination of GLP-1 RAs with glucagon (GCG) receptor agonists also has garnered interest.

In a phase 2 trial, adults with biopsy-confirmed MASH and fibrosis stages F1-F3 were randomly assigned to receive either one of three doses of the GLP-1/GCG RA survodutide (2.4, 4.8, or 6 mg) or placebo. Survodutide at each dose was found to be superior to placebo in improving MASH without the worsening of fibrosis, reducing liver fat content by at least 30%, and decreasing liver fibrosis by at least one stage, with the 4.8-mg dose showing the best performance for each measure. However, adverse events, including nausea, diarrhea, and vomiting, were more frequent with survodutide than with placebo.

Trials of triple-action agents (GLP-1/GIP/GCG RAs) are underway too.

The hope is the triple agonists could deliver greater reduction in hepatic fat in patients with MASLD, Sanyal said. 

Sanyal further noted that a reduction in liver fat is important, citing a meta-analysis that showed ≥ 30% relative decline in liver fat is associated with higher odds of histologic response and MASH resolution.

Sanyal pointed to efocipegtrutide (HM15211), a GLP-1/GIP/GCG RA, which demonstrated significant liver fat reduction after 12 weeks in patients with MASLD in a phase 1b/2a randomized, placebo-controlled trial and is now in phase 2 development.

Another example is retatrutide (LY3437943), a once-weekly injectable, that was associated with up to a 24.2% reduction in body weight at 48 weeks, compared with 2.1% with placebo, in a phase 2 trial involving patients with obesity.

A sub-study assessed the mean relative change from baseline in liver fat at 24 weeks. These participants, who also had MASLD and ≥ 10% of liver fat content, were randomly assigned to receive either retatrutide in one of four doses (1, 4, 8, or 12 mg) or placebo for 48 weeks. All doses of retatrutide showed significantly greater reduction in liver fat content compared with placebo in weeks 24-48, with a mean relative liver fat reduction > 80% at the two higher doses. Moreover, ≥ 80% of participants on the higher retatrutide doses experienced ≥ 70% reduction in liver fat at 48 weeks, compared with 0% reduction in those on placebo, and hepatic steatosis resolved in > 85% of these participants.

This space “continues to evolve at a rapid rate,” Sanyal said. For example, oral dual-action agents are under development.
 

Obstacles and Warnings

Sanyal warned that GLP-1 RAs can cause nausea, so they have to be introduced at a low dose and slowly titrated upward. They should be used with caution in people with a history of multiple endocrine neoplasia. There is also a small but increased risk for gallstone formation and gallstone-induced pancreatitis with rapid weight loss.

GLP-1 RAs may increase the risk for suicidal ideation, with the authors of a recent study calling for “urgent clarification” regarding this possibility.

Following reports of suicidality submitted through its Adverse Events Reporting System, the FDA concluded that it could find no causal relationship between these agents and increased risk for suicidal ideation but also that it could not “definitively rule out that a small risk may exist” and would continue to investigate.

Access to GLP-1 RAs is an obstacle as well. Semaglutide continues to be on the FDA’s shortage list.

“This is improving, but there are still issues around getting approval from insurance companies,” Sanyal said.

Many patients discontinue use because of tolerability or access issues, which is problematic because most regain the weight they had lost while on the medication.

“Right now, we see GLP-1 RAs as a long-term therapeutic commitment, but there is a lot of research interest in figuring out if there’s a more modest benefit — almost an induction-remission maintenance approach to weight loss,” Sanyal said. These are “evolving trends,” and it’s unclear how they will unfold.

“As of now, you have to decide that if you’re putting your patient on these medications, they will have to take them on a long-term basis and include that consideration in your risk-benefit analysis, together with any concerns about adverse effects,” he said.

Sanyal reported consulting for Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Said received research support from Exact Sciences, Boehringer Ingelheim, and Mallinckrodt.
 

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

CHICAGO — Patients who are new users of glucagon-like peptide 1 (GLP-1) receptor agonists have a low absolute risk of thyroid cancer, according to a new study presented at the annual meeting of the American Thyroid Association (ATA).

The study, presented by Juan Brito Campana, MBBS, of the Mayo Clinic in Rochester, Minnesota, used Medicare records to perform a secondary analysis of 41,000 adults with type 2 diabetes and moderate cardiovascular risk who were new users of GLP-1 receptor agonists, compared to users of other diabetes medications. 

“We took the innovative approach of applying the methodological rigor of a randomized clinical trial to the very large dataset of observational studies,” said Brito Campana.

The results showed a low absolute risk of thyroid cancer, with only 0.17% of patients in the GLP-1 group developing the disease. However, the data also showed a potential relative increase in risk during the first year of GLP-1 receptor agonist use. 

“This is likely due to increased detection rather than true incidence, as the latency period for thyroid cancer development is typically longer,” Brito Campana said. 

“We also note the limitations of the observational study design, including the short follow-up period and lack of detailed histological data. However, we believe the benefits of GLP-1 receptor agonists likely outweigh the risk of thyroid cancer.”
 

Malignancy in Bethesda III and IV Thyroid Nodules

At the same ATA session, Sapir Nachum Goldberg, MD, of the University of Pennsylvania, Philadelphia, presented the results of a retrospective record review that examined the prevalence of malignancy in Bethesda III and IV thyroid nodules with negative Thyrogen Receptor Signaling (ThyroSeq) version 3 molecular testing results.

Goldberg reported that 87% of patients with ThyroSeq negative subtype results were managed nonoperatively. “Based on our data, the true prevalence of malignancy likely lies between our low and high estimates of 3% and 23%,” she said. “We believe that the prevalence of malignancy may be higher in real-world practice than validation studies.”

Additionally, nodules with “currently negative” or “negative but limited” ThyroSeq results had a higher prevalence of malignancy (7%), compared with those with a “negative” result (2%). Factors like immediate vs delayed surgery, nodule size, and ultrasound pattern did not significantly impact malignancy prevalence.

The study results also indicated that surveillance ultrasonography is not routinely performed in up to one-third of patients, Goldberg said.

She closed by suggesting that colleagues consider the negative subtype in clinical decision-making. For “negative but limited” nodules, repeat the fine needle aspiration and, for “negative” and “currently negative” nodules, consider ultrasound follow-up as per ATA guidelines for Bethesda II cytology, she said.
 

RET-Mutated Medullary Thyroid Cancer

For patients with RET-mutated medullary thyroid cancer, Julien Hadoux, MD, PhD, of Institut de Cancérologie Gustave Roussy, Villejuif, France, presented a combined analysis of the efficacy of the RET inhibitor selpercatinib from the phase 1/2 LIBRETTO-001 and phase 3 LIBRETTO-531 trials.

This post hoc analysis used a combined cohort of 509 patients with RET-mutated advanced or metastatic medullary thyroid cancer who had received selpercatinib in the two trials.

Hadoux reported that robust and durable responses were seen across all mutation groups, including M918T, extracellular cysteine, and an “other” group composed of various uncommon RET mutations. “The median [progression-free survival] PFS was not reached for either the M918T or extracellular groups and it was 51.4 months for the Other group,” he said. 

“Selpercatinib showed superior median PFS vs control, regardless of the RET mutation. This analysis constitutes the largest catalog of RET mutations in medullary thyroid cancers treated with RET-specific inhibitors.”
 

TRK-Fusion Differentiated Thyroid Cancer

Steven Waguespack, MD, of the University of Texas MD Anderson Cancer Center, Houston, shared updated efficacy and safety data from three phase 1/2 pooled clinical trials of the tropomyosin kinase receptor (TRK) inhibitor larotrectinib in thyroid cancer. These data updated results initially published in 2022.

“Larotrectinib continues to demonstrate rapid and durable responses, extended survival, and offers a favorable safety profile in patients with TRK fusion differentiated thyroid cancer, with limited activity in anaplastic thyroid cancer,” Waguespack said. 

“Additionally, in a subset of patients, we identified some acquired on-target NTRK mutations and off-target GNAS and TP53 mutations that may give further insight into mechanisms of resistance.”

The primary endpoint was the investigator-assessed objective response rate (ORR); at 48 months, the ORR was 79% by independent review. The median PFS in patients with TRK fusion differentiated thyroid cancer was 44 months, while the median duration of response was 41 months. The 4-year overall survival rate was 86%.

Waguespack closed with a cautionary note to colleagues: “While circulating tumor DNA next-generation sequencing (NGS) analysis can be used to test for NTRK gene fusions, negative results should be followed up with tissue-based NGS,” he said.

Brito Campana and Goldberg disclosed no relevant financial relationships. Hadoux reported receiving honoraria for speaker engagements, advisory roles, or funding for CME from Eli Lilly, AAA, IPSEN, Roche, Pharma Mar, and EISAI, and research grants from Novartis, Sanofi, and Eli Lilly.

A version of this article appeared on Medscape.com.

CHICAGO — Patients who are new users of glucagon-like peptide 1 (GLP-1) receptor agonists have a low absolute risk of thyroid cancer, according to a new study presented at the annual meeting of the American Thyroid Association (ATA).

The study, presented by Juan Brito Campana, MBBS, of the Mayo Clinic in Rochester, Minnesota, used Medicare records to perform a secondary analysis of 41,000 adults with type 2 diabetes and moderate cardiovascular risk who were new users of GLP-1 receptor agonists, compared to users of other diabetes medications. 

“We took the innovative approach of applying the methodological rigor of a randomized clinical trial to the very large dataset of observational studies,” said Brito Campana.

The results showed a low absolute risk of thyroid cancer, with only 0.17% of patients in the GLP-1 group developing the disease. However, the data also showed a potential relative increase in risk during the first year of GLP-1 receptor agonist use. 

“This is likely due to increased detection rather than true incidence, as the latency period for thyroid cancer development is typically longer,” Brito Campana said. 

“We also note the limitations of the observational study design, including the short follow-up period and lack of detailed histological data. However, we believe the benefits of GLP-1 receptor agonists likely outweigh the risk of thyroid cancer.”
 

Malignancy in Bethesda III and IV Thyroid Nodules

At the same ATA session, Sapir Nachum Goldberg, MD, of the University of Pennsylvania, Philadelphia, presented the results of a retrospective record review that examined the prevalence of malignancy in Bethesda III and IV thyroid nodules with negative Thyrogen Receptor Signaling (ThyroSeq) version 3 molecular testing results.

Goldberg reported that 87% of patients with ThyroSeq negative subtype results were managed nonoperatively. “Based on our data, the true prevalence of malignancy likely lies between our low and high estimates of 3% and 23%,” she said. “We believe that the prevalence of malignancy may be higher in real-world practice than validation studies.”

Additionally, nodules with “currently negative” or “negative but limited” ThyroSeq results had a higher prevalence of malignancy (7%), compared with those with a “negative” result (2%). Factors like immediate vs delayed surgery, nodule size, and ultrasound pattern did not significantly impact malignancy prevalence.

The study results also indicated that surveillance ultrasonography is not routinely performed in up to one-third of patients, Goldberg said.

She closed by suggesting that colleagues consider the negative subtype in clinical decision-making. For “negative but limited” nodules, repeat the fine needle aspiration and, for “negative” and “currently negative” nodules, consider ultrasound follow-up as per ATA guidelines for Bethesda II cytology, she said.
 

RET-Mutated Medullary Thyroid Cancer

For patients with RET-mutated medullary thyroid cancer, Julien Hadoux, MD, PhD, of Institut de Cancérologie Gustave Roussy, Villejuif, France, presented a combined analysis of the efficacy of the RET inhibitor selpercatinib from the phase 1/2 LIBRETTO-001 and phase 3 LIBRETTO-531 trials.

This post hoc analysis used a combined cohort of 509 patients with RET-mutated advanced or metastatic medullary thyroid cancer who had received selpercatinib in the two trials.

Hadoux reported that robust and durable responses were seen across all mutation groups, including M918T, extracellular cysteine, and an “other” group composed of various uncommon RET mutations. “The median [progression-free survival] PFS was not reached for either the M918T or extracellular groups and it was 51.4 months for the Other group,” he said. 

“Selpercatinib showed superior median PFS vs control, regardless of the RET mutation. This analysis constitutes the largest catalog of RET mutations in medullary thyroid cancers treated with RET-specific inhibitors.”
 

TRK-Fusion Differentiated Thyroid Cancer

Steven Waguespack, MD, of the University of Texas MD Anderson Cancer Center, Houston, shared updated efficacy and safety data from three phase 1/2 pooled clinical trials of the tropomyosin kinase receptor (TRK) inhibitor larotrectinib in thyroid cancer. These data updated results initially published in 2022.

“Larotrectinib continues to demonstrate rapid and durable responses, extended survival, and offers a favorable safety profile in patients with TRK fusion differentiated thyroid cancer, with limited activity in anaplastic thyroid cancer,” Waguespack said. 

“Additionally, in a subset of patients, we identified some acquired on-target NTRK mutations and off-target GNAS and TP53 mutations that may give further insight into mechanisms of resistance.”

The primary endpoint was the investigator-assessed objective response rate (ORR); at 48 months, the ORR was 79% by independent review. The median PFS in patients with TRK fusion differentiated thyroid cancer was 44 months, while the median duration of response was 41 months. The 4-year overall survival rate was 86%.

Waguespack closed with a cautionary note to colleagues: “While circulating tumor DNA next-generation sequencing (NGS) analysis can be used to test for NTRK gene fusions, negative results should be followed up with tissue-based NGS,” he said.

Brito Campana and Goldberg disclosed no relevant financial relationships. Hadoux reported receiving honoraria for speaker engagements, advisory roles, or funding for CME from Eli Lilly, AAA, IPSEN, Roche, Pharma Mar, and EISAI, and research grants from Novartis, Sanofi, and Eli Lilly.

A version of this article appeared on Medscape.com.

CHICAGO — Patients who are new users of glucagon-like peptide 1 (GLP-1) receptor agonists have a low absolute risk of thyroid cancer, according to a new study presented at the annual meeting of the American Thyroid Association (ATA).

The study, presented by Juan Brito Campana, MBBS, of the Mayo Clinic in Rochester, Minnesota, used Medicare records to perform a secondary analysis of 41,000 adults with type 2 diabetes and moderate cardiovascular risk who were new users of GLP-1 receptor agonists, compared to users of other diabetes medications. 

“We took the innovative approach of applying the methodological rigor of a randomized clinical trial to the very large dataset of observational studies,” said Brito Campana.

The results showed a low absolute risk of thyroid cancer, with only 0.17% of patients in the GLP-1 group developing the disease. However, the data also showed a potential relative increase in risk during the first year of GLP-1 receptor agonist use. 

“This is likely due to increased detection rather than true incidence, as the latency period for thyroid cancer development is typically longer,” Brito Campana said. 

“We also note the limitations of the observational study design, including the short follow-up period and lack of detailed histological data. However, we believe the benefits of GLP-1 receptor agonists likely outweigh the risk of thyroid cancer.”
 

Malignancy in Bethesda III and IV Thyroid Nodules

At the same ATA session, Sapir Nachum Goldberg, MD, of the University of Pennsylvania, Philadelphia, presented the results of a retrospective record review that examined the prevalence of malignancy in Bethesda III and IV thyroid nodules with negative Thyrogen Receptor Signaling (ThyroSeq) version 3 molecular testing results.

Goldberg reported that 87% of patients with ThyroSeq negative subtype results were managed nonoperatively. “Based on our data, the true prevalence of malignancy likely lies between our low and high estimates of 3% and 23%,” she said. “We believe that the prevalence of malignancy may be higher in real-world practice than validation studies.”

Additionally, nodules with “currently negative” or “negative but limited” ThyroSeq results had a higher prevalence of malignancy (7%), compared with those with a “negative” result (2%). Factors like immediate vs delayed surgery, nodule size, and ultrasound pattern did not significantly impact malignancy prevalence.

The study results also indicated that surveillance ultrasonography is not routinely performed in up to one-third of patients, Goldberg said.

She closed by suggesting that colleagues consider the negative subtype in clinical decision-making. For “negative but limited” nodules, repeat the fine needle aspiration and, for “negative” and “currently negative” nodules, consider ultrasound follow-up as per ATA guidelines for Bethesda II cytology, she said.
 

RET-Mutated Medullary Thyroid Cancer

For patients with RET-mutated medullary thyroid cancer, Julien Hadoux, MD, PhD, of Institut de Cancérologie Gustave Roussy, Villejuif, France, presented a combined analysis of the efficacy of the RET inhibitor selpercatinib from the phase 1/2 LIBRETTO-001 and phase 3 LIBRETTO-531 trials.

This post hoc analysis used a combined cohort of 509 patients with RET-mutated advanced or metastatic medullary thyroid cancer who had received selpercatinib in the two trials.

Hadoux reported that robust and durable responses were seen across all mutation groups, including M918T, extracellular cysteine, and an “other” group composed of various uncommon RET mutations. “The median [progression-free survival] PFS was not reached for either the M918T or extracellular groups and it was 51.4 months for the Other group,” he said. 

“Selpercatinib showed superior median PFS vs control, regardless of the RET mutation. This analysis constitutes the largest catalog of RET mutations in medullary thyroid cancers treated with RET-specific inhibitors.”
 

TRK-Fusion Differentiated Thyroid Cancer

Steven Waguespack, MD, of the University of Texas MD Anderson Cancer Center, Houston, shared updated efficacy and safety data from three phase 1/2 pooled clinical trials of the tropomyosin kinase receptor (TRK) inhibitor larotrectinib in thyroid cancer. These data updated results initially published in 2022.

“Larotrectinib continues to demonstrate rapid and durable responses, extended survival, and offers a favorable safety profile in patients with TRK fusion differentiated thyroid cancer, with limited activity in anaplastic thyroid cancer,” Waguespack said. 

“Additionally, in a subset of patients, we identified some acquired on-target NTRK mutations and off-target GNAS and TP53 mutations that may give further insight into mechanisms of resistance.”

The primary endpoint was the investigator-assessed objective response rate (ORR); at 48 months, the ORR was 79% by independent review. The median PFS in patients with TRK fusion differentiated thyroid cancer was 44 months, while the median duration of response was 41 months. The 4-year overall survival rate was 86%.

Waguespack closed with a cautionary note to colleagues: “While circulating tumor DNA next-generation sequencing (NGS) analysis can be used to test for NTRK gene fusions, negative results should be followed up with tissue-based NGS,” he said.

Brito Campana and Goldberg disclosed no relevant financial relationships. Hadoux reported receiving honoraria for speaker engagements, advisory roles, or funding for CME from Eli Lilly, AAA, IPSEN, Roche, Pharma Mar, and EISAI, and research grants from Novartis, Sanofi, and Eli Lilly.

A version of this article appeared on Medscape.com.