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Abstract
PURPOSE: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective and commonly used agents in treating type 2 diabetes and obesity. Due to their success in weight loss, usage of this class of medications is becoming more common. Yet any use of GLP-1 RAs does not come without disadvantages. This meta-analysis aimed to analyze the gastrointestinal (GI)-related adverse effects (AEs) of GLP-1 RAs use. METHODS: A systematic review search following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was performed in three databases for studies reporting GI AEs after GLP-1 RA usage. A pair-wise meta-analysis evaluating the six most common GI AEs (nausea, vomiting, diarrhea, constipation, decreased appetite, and pancreatitis) among GLP-1 RAs was performed, along with a network meta-analysis comparing semaglutide, liraglutide, exenatide, dulaglutide, and tirzepatide to one another in the context of GI AEs. RESULTS: 101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies). All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and pancreatitis (2.24; 1.07%). Head-to-head comparisons revealed tirzepatide to carry the highest risk ratios for nausea and diarrhea while semaglutide carries the highest risk ratios for vomiting and constipation. CONCLUSIONS: Regardless of the GLP-1 RAs used, it is apparent that GI AEs are significant and highly prevalent. Thus, it is crucial that patients and providers alike are aware of these AEs when considering their use.