Obesity

This transcript has been edited for clarity. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This transcript has been edited for clarity. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This transcript has been edited for clarity. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

Occam’s Razor and Simple Diagnoses

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

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

 

Beyond Hickam’s Dictum and Occam’s Razor

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

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

1. Incidentaloma: An asymptomatic condition discovered accidentally.

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

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

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

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

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

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

 

Practical Insights

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

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

 

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

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

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

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

 

Occam’s Razor and Simple Diagnoses

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

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

 

Beyond Hickam’s Dictum and Occam’s Razor

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

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

1. Incidentaloma: An asymptomatic condition discovered accidentally.

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

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

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

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

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

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

 

Practical Insights

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

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

 

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

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

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

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

 

Occam’s Razor and Simple Diagnoses

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

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

 

Beyond Hickam’s Dictum and Occam’s Razor

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

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

1. Incidentaloma: An asymptomatic condition discovered accidentally.

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

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

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

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

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

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

 

Practical Insights

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

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

 

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

 

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

 

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

 

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

 

SOURCE:

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

 

LIMITATIONS:

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

 

DISCLOSURES:

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

 

SOURCE:

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

 

LIMITATIONS:

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

 

DISCLOSURES:

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

 

SOURCE:

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

 

LIMITATIONS:

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

 

DISCLOSURES:

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

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

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

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

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

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

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

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

The decision to prescribe a compounded or brand-name glucagon-like peptide 1 (GLP-1) medication for obesity treatment was never simple, but recent developments have complicated it further.

Both Eli Lilly and Novo Nordisk have asked the Food and Drug Administration (FDA) to place their GLP-1 medications, tirzepatide and semaglutide, on its Demonstrable Difficulties for Compounding or DDC Lists, which would prohibit compounding the medications. Lawsuits are another issue. The Outsourcing Facility Association, a trade group, filed a lawsuit against the FDA, calling on it to restore tirzepatide to the shortage list after the FDA removed it on October 2, despite pharmacies still experiencing shortages, according to the association. The FDA is reevaluating the decision and won’t take action against compounders in the interim, with a joint status report scheduled for November 21.

In the midst of the lawsuits and pending decisions, healthcare providers are taking a variety of approaches when they need to decide between compounded vs brand-name GLP-1s for obesity treatment. The Alliance for Pharmacy Compounding, another trade group, offers a number of suggestions for doctors faced with compound or brand-name decisions and has a website tool to be sure a compounding pharmacy meets standards.

According to the FDA, a drug may be compounded for a patient who can’t be treated with an FDA-approved medication, such as a patient who has an allergy to a certain ingredient and needs medication to be made without it, or for a medication that appears on the FDA Drug Shortages List.

Here’s how five healthcare providers make the decision.

 

Physicians Weigh in

Hard pass: “I have no experience with compounded formulations by choice,” said W. Timothy Garvey, MD, MACE, an obesity specialist and the Charles E. Butterworth Jr professor and university professor at the University of Alabama at Birmingham. “I think our patients deserve better.”

However, he acknowledged: “This is a difficult situation when there is a lack of access to medications patients need.” Even so, “online prescriptions [for compounded medications] are often done without an evaluation for obesity complications and related diseases and ongoing active management, making a complications-centric approach to care impossible.”

That’s not the optimal approach to treating obesity or other chronic diseases, he said in an interview.

Rather than prescribe compounded GLP-1s for weight loss, he said, other options exist. Among them: Prescribe Ozempic off label for obesity.

“Plus, we have a good first-generation obesity medication — phentermine/topiramate — that gets close to 10% weight loss on average in clinical trials that is available and less expensive.”

Other options, he said, are to switch to lower doses of the brand name that may be available until the treatment dose needed is out of shortage status or, the less desirable option, wait for availability, which means the patient may be off the medication for a month or more.

He acknowledged none of these options solves “the problem of high costs [for brand-name drugs] and lack of insurance coverage.”

In agreement is Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

“Doctors who are obesity medicine specialists like myself in academic centers do not prescribe compounded semaglutide or tirzepatide,” she said.

Many of the compounded prescriptions, she said, come from telehealth virtual–only companies interested in profits.

Brand names preferred: “Brand-name versions as far as I’m concerned are always preferred,” said Sarah Stombaugh, MD, an obesity medicine and family medicine physician in Charlottesville, Virginia. She terms it irresponsible for a prescriber to give a patient a compounded GLP-1 if the patient has prescription coverage and the brand name is available.

Her approach: She first checks the patients’ coverage. Do they have coverage for these medications for obesity? If so, she said, she will do a prior authorization to get the brand name approved. If a brand name is available but not covered, she explores other options. One is the cash pay option for Zepbound in vials. It’s more affordable than the typical $1000 cash price for the brand name GLP-1s but still pricey, at about $400-$549 for lower doses.

She looks at drug makers’ discount coupons, or whether a patient with a history of cardiovascular issues might qualify for coverage on Wegovy. Another option is to give the patient a prescription for Mounjaro or Ozempic to fill from a Canadian pharmacy for about $400 a month.

“I think a lot of people jump quickly to compounding,” she said.

She views it as a last resort and reminds other healthcare providers that the compounded medications aren’t cheap, either, typically costing $100-$500 a month depending on dosage. And, she said, “we have many who get the brand name for $25 a month [by using discount cards and insurance coverage].”

When prescribing a compounded medication is necessary, it’s important for healthcare providers to know that the quality of the compounding pharmacies varies greatly, Stombaugh said. A prescriber needs to pick the compounding pharmacy, not the patient, and needs to vet it, she said, asking about protocols it follows for sterility and for chemical analysis, for instance.

Stombaugh is hopeful that several new medications under study and now in phase 3 trials will soon provide enough competition to drive down the price of the current brand-name GLP-1s.

History of mistrust: Robert Dubin, MD, associate professor of research at the Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and program director for its obesity medicine fellowship, sees a role for compounding and has for several years, but acknowledged that many in his community are against it.

He estimates that about 75% of his colleagues in the Baton Rouge area are opposed to prescribing compounded GLP-1s. He chalks it up to a “track record of distrust,” based on reports of infractions called out by the FDA for some compounding pharmacies as well as physicians not being familiar with the process.

Dubin said he will prescribe a compounded medication if the brand name isn’t available. Cost is also a consideration. “If there’s not a problem with availability and there’s not a problem with cost, then why compound?”

For anyone considering prescribing compounded GLP-1s, he said, “The first step, I believe, is having a relationship with the compounding pharmacy. If you don’t have that, it could be very difficult. We don’t want to send people to a black hole, and we aren’t sure what is going to happen.” He urges colleagues to educate themselves about compounding pharmacies.

Official shortage list vs real world: “The official shortage list doesn’t always reflect the real world,” said Amanda Guarniere, NP, a nurse practitioner with a self-pay telehealth and in-person practice and director of growth for Collaborating Docs, a service based in Arlington, Virginia, that pairs nurse practitioners with supervising physicians.

“When Zepbound and Mounjaro came off the [FDA] shortage list a few weeks ago, patients were still calling around and couldn’t find it in their county.”

It’s important to vet compounding pharmacies before dealing with them, she said.

“I have accounts with two compounding pharmacies who I trust,” she said. She’s researched their quality control provided and is comfortable with their standards. When appropriate, the cost savings of compounded GLP-1s over brand name is “pretty significant,” with compounded medicine costs about 20% of brand-name costs.

When the brand name is back, how might a prescriber still write a prescription for a compounded version? “Compounded versions are typically compounded with something else,” Guarniere said.

For instance, compounded tirzepatide often includes vitamin B12 and other B vitamins, which may help with the side effect of nausea. So a prescriber might decide that the compounded prescription is more appropriate and justified because the patient would benefit from the additive, she said.

 

What Else to Know: Alliance Views

On November 7, the Alliance for Pharmacy Compounding, a trade group, responded to Lilly’s request to put tirzepatide on the “demonstrably difficult to compound (DDC)” list, asking the FDA to deny it. The group also took issue with criticism of compounded GLP-1s from the Novo Nordisk CEO.

The alliance offers perspective and a number of suggestions for doctors faced with compound or brand-name decisions, including using its website tool called “Is It Legit?” to be sure a compounding pharmacy meets standards.

“When these [GLP-1] drugs came out, I don’t think anybody anticipated them to be such blockbusters,” said Tenille Davis, PharmD, a board-certified sterile compounding pharmacist and chief advocacy officer for the Alliance for Pharmacy Compounding. Shortages have plagued the GLP-1s since their approvals, with Wegovy approved on June 4, 2021, and Eli Lilly’s Zepbound on November 8, 2023.

The proposed “Demonstrably Difficult to Compound (DDC)” rule, published in March 2024, aims to finalize the six criteria for a medication to land on that list, she said. No drugs are currently on this list, Davis said.

For now, she said, prescribers faced with a compound vs brand-name decision should be aware of the pending lawsuit concerning tirzepatide and that the FDA has said it will cease most enforcement action until 2 weeks after it reviews the decision to remove the medication from the shortage list and issues a new determination.

Davis suggests prescribers have conversations now with their patients about their options and to tell them it may be necessary to transition from the compounded medicines to brand name. “This may require insurance prior authorizations, so if they are going to transition from compounded tirzepatide to Zepbound and Mounjaro, it’s good to start the process sooner rather than later so there isn’t an interruption in care.”

Earlier in 2024, the three leading obesity organizations issued a statement, advising patients that they do not recommend the use of compounded GLP-1s.

Garvey is a consultant on advisory boards for Eli Lilly, Novo Nordisk, and several other pharmaceutical companies. Apovian had no relevant disclosures. Stombaugh, Dubin, and Guarniere had no disclosures.

A version of this article appeared on Medscape.com.

The decision to prescribe a compounded or brand-name glucagon-like peptide 1 (GLP-1) medication for obesity treatment was never simple, but recent developments have complicated it further.

Both Eli Lilly and Novo Nordisk have asked the Food and Drug Administration (FDA) to place their GLP-1 medications, tirzepatide and semaglutide, on its Demonstrable Difficulties for Compounding or DDC Lists, which would prohibit compounding the medications. Lawsuits are another issue. The Outsourcing Facility Association, a trade group, filed a lawsuit against the FDA, calling on it to restore tirzepatide to the shortage list after the FDA removed it on October 2, despite pharmacies still experiencing shortages, according to the association. The FDA is reevaluating the decision and won’t take action against compounders in the interim, with a joint status report scheduled for November 21.

In the midst of the lawsuits and pending decisions, healthcare providers are taking a variety of approaches when they need to decide between compounded vs brand-name GLP-1s for obesity treatment. The Alliance for Pharmacy Compounding, another trade group, offers a number of suggestions for doctors faced with compound or brand-name decisions and has a website tool to be sure a compounding pharmacy meets standards.

According to the FDA, a drug may be compounded for a patient who can’t be treated with an FDA-approved medication, such as a patient who has an allergy to a certain ingredient and needs medication to be made without it, or for a medication that appears on the FDA Drug Shortages List.

Here’s how five healthcare providers make the decision.

 

Physicians Weigh in

Hard pass: “I have no experience with compounded formulations by choice,” said W. Timothy Garvey, MD, MACE, an obesity specialist and the Charles E. Butterworth Jr professor and university professor at the University of Alabama at Birmingham. “I think our patients deserve better.”

However, he acknowledged: “This is a difficult situation when there is a lack of access to medications patients need.” Even so, “online prescriptions [for compounded medications] are often done without an evaluation for obesity complications and related diseases and ongoing active management, making a complications-centric approach to care impossible.”

That’s not the optimal approach to treating obesity or other chronic diseases, he said in an interview.

Rather than prescribe compounded GLP-1s for weight loss, he said, other options exist. Among them: Prescribe Ozempic off label for obesity.

“Plus, we have a good first-generation obesity medication — phentermine/topiramate — that gets close to 10% weight loss on average in clinical trials that is available and less expensive.”

Other options, he said, are to switch to lower doses of the brand name that may be available until the treatment dose needed is out of shortage status or, the less desirable option, wait for availability, which means the patient may be off the medication for a month or more.

He acknowledged none of these options solves “the problem of high costs [for brand-name drugs] and lack of insurance coverage.”

In agreement is Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

“Doctors who are obesity medicine specialists like myself in academic centers do not prescribe compounded semaglutide or tirzepatide,” she said.

Many of the compounded prescriptions, she said, come from telehealth virtual–only companies interested in profits.

Brand names preferred: “Brand-name versions as far as I’m concerned are always preferred,” said Sarah Stombaugh, MD, an obesity medicine and family medicine physician in Charlottesville, Virginia. She terms it irresponsible for a prescriber to give a patient a compounded GLP-1 if the patient has prescription coverage and the brand name is available.

Her approach: She first checks the patients’ coverage. Do they have coverage for these medications for obesity? If so, she said, she will do a prior authorization to get the brand name approved. If a brand name is available but not covered, she explores other options. One is the cash pay option for Zepbound in vials. It’s more affordable than the typical $1000 cash price for the brand name GLP-1s but still pricey, at about $400-$549 for lower doses.

She looks at drug makers’ discount coupons, or whether a patient with a history of cardiovascular issues might qualify for coverage on Wegovy. Another option is to give the patient a prescription for Mounjaro or Ozempic to fill from a Canadian pharmacy for about $400 a month.

“I think a lot of people jump quickly to compounding,” she said.

She views it as a last resort and reminds other healthcare providers that the compounded medications aren’t cheap, either, typically costing $100-$500 a month depending on dosage. And, she said, “we have many who get the brand name for $25 a month [by using discount cards and insurance coverage].”

When prescribing a compounded medication is necessary, it’s important for healthcare providers to know that the quality of the compounding pharmacies varies greatly, Stombaugh said. A prescriber needs to pick the compounding pharmacy, not the patient, and needs to vet it, she said, asking about protocols it follows for sterility and for chemical analysis, for instance.

Stombaugh is hopeful that several new medications under study and now in phase 3 trials will soon provide enough competition to drive down the price of the current brand-name GLP-1s.

History of mistrust: Robert Dubin, MD, associate professor of research at the Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and program director for its obesity medicine fellowship, sees a role for compounding and has for several years, but acknowledged that many in his community are against it.

He estimates that about 75% of his colleagues in the Baton Rouge area are opposed to prescribing compounded GLP-1s. He chalks it up to a “track record of distrust,” based on reports of infractions called out by the FDA for some compounding pharmacies as well as physicians not being familiar with the process.

Dubin said he will prescribe a compounded medication if the brand name isn’t available. Cost is also a consideration. “If there’s not a problem with availability and there’s not a problem with cost, then why compound?”

For anyone considering prescribing compounded GLP-1s, he said, “The first step, I believe, is having a relationship with the compounding pharmacy. If you don’t have that, it could be very difficult. We don’t want to send people to a black hole, and we aren’t sure what is going to happen.” He urges colleagues to educate themselves about compounding pharmacies.

Official shortage list vs real world: “The official shortage list doesn’t always reflect the real world,” said Amanda Guarniere, NP, a nurse practitioner with a self-pay telehealth and in-person practice and director of growth for Collaborating Docs, a service based in Arlington, Virginia, that pairs nurse practitioners with supervising physicians.

“When Zepbound and Mounjaro came off the [FDA] shortage list a few weeks ago, patients were still calling around and couldn’t find it in their county.”

It’s important to vet compounding pharmacies before dealing with them, she said.

“I have accounts with two compounding pharmacies who I trust,” she said. She’s researched their quality control provided and is comfortable with their standards. When appropriate, the cost savings of compounded GLP-1s over brand name is “pretty significant,” with compounded medicine costs about 20% of brand-name costs.

When the brand name is back, how might a prescriber still write a prescription for a compounded version? “Compounded versions are typically compounded with something else,” Guarniere said.

For instance, compounded tirzepatide often includes vitamin B12 and other B vitamins, which may help with the side effect of nausea. So a prescriber might decide that the compounded prescription is more appropriate and justified because the patient would benefit from the additive, she said.

 

What Else to Know: Alliance Views

On November 7, the Alliance for Pharmacy Compounding, a trade group, responded to Lilly’s request to put tirzepatide on the “demonstrably difficult to compound (DDC)” list, asking the FDA to deny it. The group also took issue with criticism of compounded GLP-1s from the Novo Nordisk CEO.

The alliance offers perspective and a number of suggestions for doctors faced with compound or brand-name decisions, including using its website tool called “Is It Legit?” to be sure a compounding pharmacy meets standards.

“When these [GLP-1] drugs came out, I don’t think anybody anticipated them to be such blockbusters,” said Tenille Davis, PharmD, a board-certified sterile compounding pharmacist and chief advocacy officer for the Alliance for Pharmacy Compounding. Shortages have plagued the GLP-1s since their approvals, with Wegovy approved on June 4, 2021, and Eli Lilly’s Zepbound on November 8, 2023.

The proposed “Demonstrably Difficult to Compound (DDC)” rule, published in March 2024, aims to finalize the six criteria for a medication to land on that list, she said. No drugs are currently on this list, Davis said.

For now, she said, prescribers faced with a compound vs brand-name decision should be aware of the pending lawsuit concerning tirzepatide and that the FDA has said it will cease most enforcement action until 2 weeks after it reviews the decision to remove the medication from the shortage list and issues a new determination.

Davis suggests prescribers have conversations now with their patients about their options and to tell them it may be necessary to transition from the compounded medicines to brand name. “This may require insurance prior authorizations, so if they are going to transition from compounded tirzepatide to Zepbound and Mounjaro, it’s good to start the process sooner rather than later so there isn’t an interruption in care.”

Earlier in 2024, the three leading obesity organizations issued a statement, advising patients that they do not recommend the use of compounded GLP-1s.

Garvey is a consultant on advisory boards for Eli Lilly, Novo Nordisk, and several other pharmaceutical companies. Apovian had no relevant disclosures. Stombaugh, Dubin, and Guarniere had no disclosures.

A version of this article appeared on Medscape.com.

The decision to prescribe a compounded or brand-name glucagon-like peptide 1 (GLP-1) medication for obesity treatment was never simple, but recent developments have complicated it further.

Both Eli Lilly and Novo Nordisk have asked the Food and Drug Administration (FDA) to place their GLP-1 medications, tirzepatide and semaglutide, on its Demonstrable Difficulties for Compounding or DDC Lists, which would prohibit compounding the medications. Lawsuits are another issue. The Outsourcing Facility Association, a trade group, filed a lawsuit against the FDA, calling on it to restore tirzepatide to the shortage list after the FDA removed it on October 2, despite pharmacies still experiencing shortages, according to the association. The FDA is reevaluating the decision and won’t take action against compounders in the interim, with a joint status report scheduled for November 21.

In the midst of the lawsuits and pending decisions, healthcare providers are taking a variety of approaches when they need to decide between compounded vs brand-name GLP-1s for obesity treatment. The Alliance for Pharmacy Compounding, another trade group, offers a number of suggestions for doctors faced with compound or brand-name decisions and has a website tool to be sure a compounding pharmacy meets standards.

According to the FDA, a drug may be compounded for a patient who can’t be treated with an FDA-approved medication, such as a patient who has an allergy to a certain ingredient and needs medication to be made without it, or for a medication that appears on the FDA Drug Shortages List.

Here’s how five healthcare providers make the decision.

 

Physicians Weigh in

Hard pass: “I have no experience with compounded formulations by choice,” said W. Timothy Garvey, MD, MACE, an obesity specialist and the Charles E. Butterworth Jr professor and university professor at the University of Alabama at Birmingham. “I think our patients deserve better.”

However, he acknowledged: “This is a difficult situation when there is a lack of access to medications patients need.” Even so, “online prescriptions [for compounded medications] are often done without an evaluation for obesity complications and related diseases and ongoing active management, making a complications-centric approach to care impossible.”

That’s not the optimal approach to treating obesity or other chronic diseases, he said in an interview.

Rather than prescribe compounded GLP-1s for weight loss, he said, other options exist. Among them: Prescribe Ozempic off label for obesity.

“Plus, we have a good first-generation obesity medication — phentermine/topiramate — that gets close to 10% weight loss on average in clinical trials that is available and less expensive.”

Other options, he said, are to switch to lower doses of the brand name that may be available until the treatment dose needed is out of shortage status or, the less desirable option, wait for availability, which means the patient may be off the medication for a month or more.

He acknowledged none of these options solves “the problem of high costs [for brand-name drugs] and lack of insurance coverage.”

In agreement is Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

“Doctors who are obesity medicine specialists like myself in academic centers do not prescribe compounded semaglutide or tirzepatide,” she said.

Many of the compounded prescriptions, she said, come from telehealth virtual–only companies interested in profits.

Brand names preferred: “Brand-name versions as far as I’m concerned are always preferred,” said Sarah Stombaugh, MD, an obesity medicine and family medicine physician in Charlottesville, Virginia. She terms it irresponsible for a prescriber to give a patient a compounded GLP-1 if the patient has prescription coverage and the brand name is available.

Her approach: She first checks the patients’ coverage. Do they have coverage for these medications for obesity? If so, she said, she will do a prior authorization to get the brand name approved. If a brand name is available but not covered, she explores other options. One is the cash pay option for Zepbound in vials. It’s more affordable than the typical $1000 cash price for the brand name GLP-1s but still pricey, at about $400-$549 for lower doses.

She looks at drug makers’ discount coupons, or whether a patient with a history of cardiovascular issues might qualify for coverage on Wegovy. Another option is to give the patient a prescription for Mounjaro or Ozempic to fill from a Canadian pharmacy for about $400 a month.

“I think a lot of people jump quickly to compounding,” she said.

She views it as a last resort and reminds other healthcare providers that the compounded medications aren’t cheap, either, typically costing $100-$500 a month depending on dosage. And, she said, “we have many who get the brand name for $25 a month [by using discount cards and insurance coverage].”

When prescribing a compounded medication is necessary, it’s important for healthcare providers to know that the quality of the compounding pharmacies varies greatly, Stombaugh said. A prescriber needs to pick the compounding pharmacy, not the patient, and needs to vet it, she said, asking about protocols it follows for sterility and for chemical analysis, for instance.

Stombaugh is hopeful that several new medications under study and now in phase 3 trials will soon provide enough competition to drive down the price of the current brand-name GLP-1s.

History of mistrust: Robert Dubin, MD, associate professor of research at the Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and program director for its obesity medicine fellowship, sees a role for compounding and has for several years, but acknowledged that many in his community are against it.

He estimates that about 75% of his colleagues in the Baton Rouge area are opposed to prescribing compounded GLP-1s. He chalks it up to a “track record of distrust,” based on reports of infractions called out by the FDA for some compounding pharmacies as well as physicians not being familiar with the process.

Dubin said he will prescribe a compounded medication if the brand name isn’t available. Cost is also a consideration. “If there’s not a problem with availability and there’s not a problem with cost, then why compound?”

For anyone considering prescribing compounded GLP-1s, he said, “The first step, I believe, is having a relationship with the compounding pharmacy. If you don’t have that, it could be very difficult. We don’t want to send people to a black hole, and we aren’t sure what is going to happen.” He urges colleagues to educate themselves about compounding pharmacies.

Official shortage list vs real world: “The official shortage list doesn’t always reflect the real world,” said Amanda Guarniere, NP, a nurse practitioner with a self-pay telehealth and in-person practice and director of growth for Collaborating Docs, a service based in Arlington, Virginia, that pairs nurse practitioners with supervising physicians.

“When Zepbound and Mounjaro came off the [FDA] shortage list a few weeks ago, patients were still calling around and couldn’t find it in their county.”

It’s important to vet compounding pharmacies before dealing with them, she said.

“I have accounts with two compounding pharmacies who I trust,” she said. She’s researched their quality control provided and is comfortable with their standards. When appropriate, the cost savings of compounded GLP-1s over brand name is “pretty significant,” with compounded medicine costs about 20% of brand-name costs.

When the brand name is back, how might a prescriber still write a prescription for a compounded version? “Compounded versions are typically compounded with something else,” Guarniere said.

For instance, compounded tirzepatide often includes vitamin B12 and other B vitamins, which may help with the side effect of nausea. So a prescriber might decide that the compounded prescription is more appropriate and justified because the patient would benefit from the additive, she said.

 

What Else to Know: Alliance Views

On November 7, the Alliance for Pharmacy Compounding, a trade group, responded to Lilly’s request to put tirzepatide on the “demonstrably difficult to compound (DDC)” list, asking the FDA to deny it. The group also took issue with criticism of compounded GLP-1s from the Novo Nordisk CEO.

The alliance offers perspective and a number of suggestions for doctors faced with compound or brand-name decisions, including using its website tool called “Is It Legit?” to be sure a compounding pharmacy meets standards.

“When these [GLP-1] drugs came out, I don’t think anybody anticipated them to be such blockbusters,” said Tenille Davis, PharmD, a board-certified sterile compounding pharmacist and chief advocacy officer for the Alliance for Pharmacy Compounding. Shortages have plagued the GLP-1s since their approvals, with Wegovy approved on June 4, 2021, and Eli Lilly’s Zepbound on November 8, 2023.

The proposed “Demonstrably Difficult to Compound (DDC)” rule, published in March 2024, aims to finalize the six criteria for a medication to land on that list, she said. No drugs are currently on this list, Davis said.

For now, she said, prescribers faced with a compound vs brand-name decision should be aware of the pending lawsuit concerning tirzepatide and that the FDA has said it will cease most enforcement action until 2 weeks after it reviews the decision to remove the medication from the shortage list and issues a new determination.

Davis suggests prescribers have conversations now with their patients about their options and to tell them it may be necessary to transition from the compounded medicines to brand name. “This may require insurance prior authorizations, so if they are going to transition from compounded tirzepatide to Zepbound and Mounjaro, it’s good to start the process sooner rather than later so there isn’t an interruption in care.”

Earlier in 2024, the three leading obesity organizations issued a statement, advising patients that they do not recommend the use of compounded GLP-1s.

Garvey is a consultant on advisory boards for Eli Lilly, Novo Nordisk, and several other pharmaceutical companies. Apovian had no relevant disclosures. Stombaugh, Dubin, and Guarniere had no disclosures.

A version of this article appeared on Medscape.com.