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Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis

A. Ismaiel, G. G. M. Scarlata, Irina Boitos, D. Leucuța, Ș. Popa, Nahlah Al Srouji, L. Abenavoli, D. Dumitrașcu

International Journal of Obesity, 2025

33,354 participants · 97 citations

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…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 33,354 participants or records.

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