Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis.

Safwan, Moaz et al.·Annals of Saudi medicine·2025·Strong Evidencesystematic review and meta-analysis
RPEP-13360Systematic review and meta AnalysisStrong Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
systematic review and meta-analysis
Evidence
Strong Evidence
Sample
N=26,894
Participants
Adults with obesity without diabetes across 13 randomized controlled trials

What This Study Found

Both semaglutide and tirzepatide nearly doubled GI side effects versus placebo. Tirzepatide had higher GI risk (RR 2.94) than semaglutide (RR 1.68). Semaglutide increased gallstone risk 2.6-fold but tirzepatide did not.

Key Numbers

13 RCTs; n=26,894; overall GI RR 1.86 (95% CI 1.56-2.21); tirzepatide GI RR 2.94 (95% CI 2.61-3.32); semaglutide GI RR 1.68 (95% CI 1.46-1.94); semaglutide cholelithiasis RR 2.6 (95% CI 1.40-4.82)

How They Did This

Systematic review and meta-analysis of RCTs comparing semaglutide or tirzepatide to placebo in obese adults without diabetes. Pooled risk ratios for GI, biliary, hepatic, and pancreatic adverse events.

Why This Research Matters

With millions using these drugs for weight loss, understanding the distinct GI safety profiles helps clinicians choose the right drug and monitor for specific complications.

What This Study Doesn't Tell Us

Trials had different follow-up durations and doses. Cannot compare semaglutide and tirzepatide directly since they were compared to placebo separately. Limited data on rare events like pancreatic cancer.

Trust & Context

Original Title:
Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis.
Published In:
Annals of Saudi medicine, 45(2), 129-143 (2025)
Database ID:
RPEP-13360

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Read More on RethinkPeptides

Cite This Study

RPEP-13360·https://rethinkpeptides.com/research/RPEP-13360

APA

Safwan, Moaz; Bourgleh, Mariam Safwan; Alotaibi, Shahad Abdullah; Alotaibi, Eman; Al-Ruqi, Abdulsalam; El Raeya, Fathiya. (2025). Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis.. Annals of Saudi medicine, 45(2), 129-143. https://doi.org/10.5144/0256-4947.2025.129

MLA

Safwan, Moaz, et al. "Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis.." Annals of Saudi medicine, 2025. https://doi.org/10.5144/0256-4947.2025.129

RethinkPeptides

RethinkPeptides Research Database. "Gastrointestinal safety of semaglutide and tirzepatide vs. p..." RPEP-13360. Retrieved from https://rethinkpeptides.com/research/safwan-2025-gastrointestinal-safety-of-semaglutide

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.