The SURMOUNT-4 Trial: What Happens When You Stop Tirzepatide

Part of the DietApp.com GLP-1 Trial Database, a comprehensive, regularly reviewed resource.

What It Is

SURMOUNT-4 is a Phase 3 randomized withdrawal trial specifically designed to test what happens after stopping tirzepatide (Zepbound). Participants first completed a 36-week open-label lead-in period on tirzepatide, then were randomly assigned to either continue tirzepatide or switch to placebo for the following 52 weeks, without knowing which group they were in.

Key Results

Participants who completed the 36-week lead-in period had already lost a mean of 20.9% of body weight. From week 36 to week 88, those who continued tirzepatide lost an additional 5.5% on average, reaching a total mean weight loss of 25.3% from the start of the study, while those switched to placebo regained a mean of 14% during the same period. By week 88, 89.5% of participants who continued tirzepatide had maintained at least 80% of their lead-in weight loss, compared to just 16.6% of those on placebo.

It Wasn't Just the Scale

A post-hoc analysis published in JAMA Internal Medicine found that participants who regained 25% or more of their lost weight after stopping also experienced a meaningful reversal of the cardiometabolic improvements, like waist circumference, cholesterol, and fasting insulin, they had gained during treatment. Participants who regained less than 25% of their weight showed changes that weren't significantly different from where they stood right before stopping.

Why This Trial Matters

SURMOUNT-4 is the most direct, purpose-built evidence behind the general understanding that GLP-1 medications function as an ongoing treatment rather than a short-course fix, discussed elsewhere in this library. It doesn't answer every individual's situation, some people maintain more of their results than others, but it removes the guesswork about what the average outcome looks like after stopping.

References

• Aronne LJ et al., SURMOUNT-4 Trial, JAMA 2023
• Horn DB et al., Cardiometabolic Parameter Change on Tirzepatide Withdrawal, JAMA Internal Medicine 2025
• HCPLive: SURMOUNT-4, Tirzepatide Withdrawal Linked to Weight Regain

Related Resources

• Tirzepatide Medication Guide
• Zepbound Medication Guide

Related Articles

• Will I Regain Weight If I Stop Taking My GLP-1 Medication?
• Is It Safe to Stop a GLP-1 Medication Suddenly?
• The SURMOUNT Trials

Explore More

Explore the full GLP-1 Tracker knowledge base on DietApp.com

Get Started

Download DietApp.com to track your own progress alongside the evidence behind your treatment.

About DietApp.com

DietApp.com combines evidence-based GLP-1 medication education with practical treatment tracking tools. The information on DietApp.com is intended for educational purposes only and should not replace professional medical advice, diagnosis, or treatment.

Last medically reviewed and updated: July 11, 2026.