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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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.
What This Study Doesn't 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.
Trust & Context
- Original Title:
- 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.
- Published In:
- Diabetes, obesity & metabolism, 27(4), 1826-1835 (2025)
- Authors:
- Rubino, Domenica M, Pedersen, Sue D, Connery, Lisa(2), Cao, Dachuang, Chigutsa, Farai, Stefanski, Adam, Fraseur Brumm, Julia, Griffin, Ryan, Gerber, Claire
- Database ID:
- RPEP-13323
Evidence Hierarchy
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Cite This Study
https://rethinkpeptides.com/research/RPEP-13323APA
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
MLA
Rubino, Domenica M, et al. "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, 2025. https://doi.org/10.1111/dom.16176
RethinkPeptides
RethinkPeptides Research Database. "Gastrointestinal tolerability and weight reduction associate..." RPEP-13323. Retrieved from https://rethinkpeptides.com/research/rubino-2025-gastrointestinal-tolerability-and-weight
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.