Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss
Open accessAbstract
This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events.
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A real-world study found increased risks of biliary disease with any GLP-1RA use compared with bupropion-naltrexone (HR 1.5; 95% CI 0.9-2.5).
“A real‐world study also found increased risks of biliary disease with any GLP‐1RA use compared with bupropion‐naltrexone (HR 1.5; 95% CI 0.9–2.5). 91”
From Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer <scp>GLP</scp> ‐ <scp>1RA</scp> ‐based weight‐loss therapies (2025) · cites this paper as [91]
Table 2 reports an adjusted HR of 1.50 (95% CI, 0.89–2.53), matching the cited numbers after rounding. But the Results and Discussion explicitly state that GLP-1 agonist use was not associated with increased risk of biliary disease; the confidence interval includes 1. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredIn populations using GLP-1 RAs in higher doses specifically for weight loss, less is currently known about pancreatitis and pancreatic cancer risks.
“In populations using GLP‐1 RAs in higher doses specifically for weight loss, less is currently known about pancreatitis and pancreatic cancer risks. 79 , 91”
From Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer <scp>GLP</scp> ‐ <scp>1RA</scp> ‐based weight‐loss therapies (2025) · cites this paper as [91]
The opening passage (page not provided) says weight-loss trials were too small and brief to capture gastrointestinal adverse events, including pancreatitis, supporting a knowledge gap for that risk. The Results and Discussion (page not provided) then report an association with pancreatitis in weight-loss users. The paper does not address pancreatic cancer or establish that these users took higher doses. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn a population using GLP-1 RAs for obesity management without history of diabetes, increased risk of pancreatitis associated with the GLP-1 RAs was found compared to bupropion-naltrexone (HR 9.1, 95% CI 1.25-66.0).
“However, in a population using GLP-1 RAs for obesity management without history of diabetes, increased risk of pancreatitis associated with the GLP-1 RAs was found compared to bupropion-naltrexone (HR 9.1, 95%CI 1.25–66.0) suggesting the risk benefit ratio of these medications is influenced by underlying disease state.69”
From GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review (2024) · cites this paper as [69]
The risk-benefit ratio of these medications is influenced by underlying disease state.
“However, in a population using GLP-1 RAs for obesity management without history of diabetes, increased risk of pancreatitis associated with the GLP-1 RAs was found compared to bupropion-naltrexone (HR 9.1, 95%CI 1.25–66.0) suggesting the risk benefit ratio of these medications is influenced by underlying disease state.69”
From GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review (2024) · cites this paper as [69]
A real-world comparative cohort study found rates of pancreatitis of 4.6 (semaglutide) and 7.9 (liraglutide) per 1000 person-years compared with 1.0 in bupropion-naltrexone initiators, yielding HR 9.1 (95% CI 1.3-66.0).
“A real‐world comparative cohort study found rates of pancreatitis of 4.6 (semaglutide) and 7.9 (liraglutide) per 1000 person‐years compared with a remarkably low rate of 1.0 in bupropion‐naltrexone initiators, yielding a high yet imprecise HR of 9.1 (95% CI 1.3–66.0). 91”
A recent real-world study of people with obesity found markedly increased rates of bowel obstruction (HR 4.22; 95% CI 1.02-17.40) and gastroparesis (3.67 [95% CI, 1.15-11.90]) with semaglutide/liraglutide versus bupropion-naltrexone.
“A recent real‐world study of people with obesity compared initiators of semaglutide and liraglutide to those initiating bupropion‐naltrexone and found markedly increased rates of bowel obstruction (hazard ratio [HR] 4.22; 95% confidence interval [CI] 1.02–17.40) and gastroparesis (3.67 [95% CI, 1.15–11.90]). 91”
Historically, pancreatitis has been a concern for IBTs.
“Historically, pancreatitis has been a concern for IBTs [91,105].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [91]
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- Authors
- Sodhi, M., Rezaeianzadeh, R., Kezouh, A., & Etminan, M.
- Affiliations
- University of British Columbia (CA)
- StatExpert Ltd, Laval, Quebec, Canada
- Corresponding author
- Etminan, Mahyar
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2023-11-14
- Volume
- 330
- Issue
- 18
- Pages
- 1795
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC10557026
- OpenAlex
- W4387357834
- Semantic Scholar
- 2ab96734748df543c66cd5be48f3199968026e1a
- Cited by
- 471
- References
- 6
- Citations by year
- 2026: 111 · 2025: 192 · 2024: 157 · 2023: 11
- FWCI
- 72.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- GLP-1 receptor agonists, semaglutide, liraglutide, weight loss, gastrointestinal adverse effects, adverse drug reactions, obesity treatment
- MeSH terms
- Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Gastrointestinal Diseases, Humans, Hypoglycemic Agents, Weight Loss, Anti-Obesity Agents, Overweight
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