Research

Hormonal

GLP-1 receptor agonists (GLP-1RAs) cause a significantly higher rate of intolerable gastrointestinal adverse reactions leading to drug withdrawal compared to other hypoglycemic agents (Insulin, SGLT2i, DPP4i, TZD) and placebo.

If you are considering a GLP-1RA, expect a higher likelihood of gastrointestinal side effects (nausea, vomiting, diarrhea) compared to other common diabetes drugs like Metformin or SGLT2 inhibitors. These side effects are the most common reason for stopping the medication. However, not all GLP-1RAs carry the same risk; Dulaglutide appears to have the lowest risk of intolerable GI reactions, while Semaglutide and Liraglutide have higher risks, especially at higher doses.

GoodSupportsHIGH confidence
GLP-1RAs showed a higher risk compared to Insulin (OR=7.54, 95%CI 3.39, 16.78), SGLT2i(OR=11.78, 95%CI 2.90, 47.90), DPP4i (OR=4.20, 95%CI 1.76, 10.05), TZD(OR=6.89, 95%CI 1.19, 39.80), Placebo(OR=4.84, 95%CI 3.45, 6.79) and Blank(OR=4.41, 95%CI 1.34, 14.58).
Ziqi Zhang et al. · Frontiers in Endocrinology · 2023

Why this rating

Based on a network meta-analysis of 64 RCTs with moderate quality evidence (GRADE).

Source

GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis

Ziqi Zhang et al. · Frontiers in Endocrinology · 2023

DOI 10.3389/fendo.2023.1149328

Meta-analysis · 64 studiesCited 38×
Read the paper
DOI resolved against Crossref · corpus check 2026-06-10

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