Study summary · research use only
Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This systematic review and dose-response network meta-analysis searched PubMed and EMBASE for randomized trials of GLP-1 receptor agonists (GLP-1 RAs) in non-diabetic adults with overweight or obesity, including Thirty-nine articles covering 33,354 individuals, quality-assessed with the Cochrane Collaboration's tool. The abstract reports nausea, vomiting, diarrhea, and constipation were the most common gastrointestinal adverse events, with orforglipron showing the highest nausea risk, followed by exenatide, tirzepatide, semaglutide, and liraglutide. Liraglutide, orforglipron, semaglutide, and tirzepatide were associated with increased vomiting risk, while cagrilinitide and exenatide were not; exenatide, cagrilinitide, and orforglipron were not associated with diarrhea risk, and semaglutide and liraglutide were associated with increased constipation risk while cagrilinitide and exenatide were not.
Abstract
Overweight and obesity are major global health issues, increasing disease risk and straining healthcare systems. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for weight loss but cause gastrointestinal side effects, affecting adherence. Research often focuses on diabetics, leaving a gap in understanding their effects on non-diabetic individuals with overweight or obesity. This systematic review and dose-response network meta-analysis addresses this gap, analyzing gastrointestinal adverse events from GLP-1 RAs in non-diabetic subjects with overweight or obesity. We evaluated available evidence by searching PubMed and EMBASE databases, according to specific inclusion and exclusion eligibility criteria to evaluate gastrointestinal adverse events associated with GLP-1 RAs in non-diabetic individuals with overweight or obesity. Quality assessment of included studies was conducted using Cochrane Collaboration's tool. Thirty-nine articles were included in the review showing a total number of 33,354 individuals. Nausea, vomiting, diarrhea, and constipation were the most common gastrointestinal adverse effects. All evaluated GLP-1 RAs led to a significant increase in nausea risk, with orforglipron showing the highest risk, followed by exenatide, tirzepatide, semaglutide, and liraglutide. Additionally, liraglutide, orforglipron, semaglutide, and tirzepatide were associated with increased vomiting risk, while cagrilinitide and exenatide showed no significant increase. Exenatide, cagrilinitide, orforglipron were not associated with diarrhea risk. Finally, semaglutide and liraglutide were associated to increased constipation risk, while cagrilinitide and exenatide showed no significant increase. GLP-1 RAs showed several adverse gastrointestinal effects in non-diabetic patients with overweight or obesity. Understanding the different risk profiles of GLP-1 RAs helps clinicians make informed treatment decisions by balancing therapeutic benefits with potential side effects.
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