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Research citation

Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials.

Post Hoc Analysis Of Randomized Controlled TrialsStrong evidence

This record provides bibliographic details and links to the original research. An editorial study breakdown is not available.

What the researchers found

GI side effects like nausea and vomiting contributed at most 3.1% of the total weight loss seen with tirzepatide across the SURMOUNT trials.

Why it matters

Some critics suggested GLP-1 drugs only work because they make people feel sick. This analysis shows tirzepatide produces nearly the same weight loss whether or not patients have GI symptoms.

The numbers in context

GI AEs in 27.8-72.8% of tirzepatide vs 12.2-32.5% of placebo; 1.0-10.5% discontinued due to GI AEs; GI mediated up to 3.1% of weight loss

How the study worked

Post hoc analysis pooling data from SURMOUNT-1 through -4 Phase 3 trials. Compared weight change by GI symptom status. Mediation analysis quantified GI contribution to weight loss.

Who was studied

Adults with obesity or overweight, with or without type 2 diabetes

What this study cannot tell us

Post hoc analysis, not prespecified. GI symptoms were self-reported. Mediation analysis assumes causal pathways that may not fully hold. Pooling across trials with different populations.

Read the original research

Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials.

Diabetes, obesity & metabolism, 27(4), 1826-1835

Citation

Rubino, Domenica M; Pedersen, Sue D; Connery, Lisa; Cao, Dachuang; Chigutsa, Farai; Stefanski, Adam; Fraseur Brumm, Julia; Griffin, Ryan; Gerber, Claire. (2025). Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials.. Diabetes, obesity & metabolism, 27(4), 1826-1835. https://doi.org/10.1111/dom.16176