Diabetes, obesity & metabolismJan 10, 2025

Tirzepatide’s effects on digestion and weight loss in adults with overweight or obesity, with and without type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 20, 2026

Abstract

GI adverse events (AEs) are associated with up to 3.1% of total weight reduction with tirzepatide.

More participants in the tirzepatide treatment arms reported gastrointestinal AEs (27.8%-72.8%) compared to placebo (12.2%-32.5%).
Most gastrointestinal AEs were non-serious and occurred during dose escalation.
Weight reduction was similar among participants reporting no nausea, nausea alone, or any gastrointestinal AEs.
Between 1.0% and 10.5% of tirzepatide-treated participants discontinued treatment due to gastrointestinal AEs.
First use of antidiarrheal and antiemetic medications was most commonly reported during dose escalation.

Simplified

AIMS: This analysis evaluated whether gastrointestinal (GI) adverse events (AEs) including nausea, vomiting, diarrhoea (N/V/D) and dyspepsia were associated with weight reduction with tirzepatide across the SURMOUNT-1 to -4 trials.

MATERIALS AND METHODS: SURMOUNT-1 to -4 were global Phase 3 clinical trials evaluating the safety and efficacy of tirzepatide among participants with obesity or overweight with or without type 2 diabetes (T2D). Participants were randomly assigned to receive once weekly subcutaneous tirzepatide or placebo. This post hoc analysis investigated weight change at the primary endpoint from baseline among participants who self-reported no N/V/D, any N/V/D or nausea alone. Mediation analyses evaluated the contribution of N/V/D and dyspepsia on weight reduction. Time to first use of antidiarrheal and antiemetic usage was reported by time intervals.

RESULTS: Baseline characteristics were similar between participants who reported N/V/D and those who did not. More participants reported GI AEs in the tirzepatide treatment arms (27.8%-72.8%) than with placebo (12.2%-32.5%). Most GI AEs were non-serious and occurred during dose escalation. Between 1.0% and 10.5% of tirzepatide-treated participants discontinued treatment due to GI AEs. Weight reduction with tirzepatide was similar among participants reporting no nausea, nausea alone, or any N/V/D. Mediation analyses suggested that N/V/D and dyspepsia were associated with up to 3.1% of total weight reduction. When required, first use of antidiarrheal and antiemetic medication was most commonly reported during dose escalation.

CONCLUSIONS: In this post hoc analysis, GI AEs appeared to contribute slightly to the weight reduction seen with tirzepatide in participants with obesity or overweight with or without T2D.

Key numbers

19.7%

Weight Reduction in Tirzepatide Participants

Mean percentage change in weight from baseline in SURMOUNT-1.

27.8% to 72.8%

GI Adverse Events Reporting

Percentage of participants reporting GI AEs in tirzepatide arms.

3.1%

Contribution of GI AEs to Weight Reduction

Estimated percentage of total weight reduction attributed to GI AEs.

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Funding

Competing interests

DMR is currently a clinical investigator for Astra Zeneca, Novo Nordisk, Boehringer Ingelheim and Kallyope; received consultant/advisor fees from Novo Nordisk, Regeneron, Boehringer Ingelheim, Shionogi, Cytoki Pharma and Eli Lilly and Company; payment or honoraria for participating as a speaker from Novo Nordisk; CME honoraria from Prime Therapeutics, Peer View, Medscape, Endocrine Society and ADA; travel support for speaking/presenting from Novo Nordisk, Boehringer Ingelheim, Eli Lilly and Company, Prime Inc., Peer View, Medscape, Endocrine Society and ADA; support for meeting registration from Endocrine Society, ADA, and The Obesity Society; medical writing support from Novo Nordisk and Boehringer Ingelheim; and is a shareholder at Eli Lilly and Company. SDP declares personal fees for advisory board membership and speaking from Abbott, AstraZeneca, Bayer, Bausch, Boehringer Ingelheim, Dexcom, Eli Lilly and Company, GSK, HLS Therapeutics, Janssen, Merck, Novo Nordisk, Pfizer, Regenron and Sanofi; consulting fees from Abbott, AstraZeneca, Dexcom, HLS Therapeutics, Janssen and Novo Nordisk; fees or grants for clinical trials from AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer, Prometic and Sanofi; grants from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company and Sanofi; and non‐financial support for travel to meetings from AstraZeneca, Bausch Health, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Novo Nordisk and Sanofi. LC declares clinical investigator activity for Eli Lilly and Company. DC, FC, AS, JFB, RG and CG are employees and shareholders of Eli Lilly and Company.

PubMed

Tirzepatide’s effects on digestion and weight loss in adults with overweight or obesity, with and without type 2 diabetes

Abstract

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Competing interests

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