What Happens When You Stop Taking Tirzepatide? The SURMOUNT-4 Weight Maintenance Trial
People who stopped tirzepatide after 36 weeks regained most of their lost weight, while those who continued treatment lost even more — reaching 25.3% total weight reduction at 88 weeks.
Quick Facts
What This Study Found
In the SURMOUNT-4 trial, adults with obesity who continued tirzepatide after an initial 36-week treatment period maintained and extended their weight loss, reaching a total reduction of 25.3% from baseline at 88 weeks. Those who switched to placebo regained most of their lost weight, ending with only 9.9% total weight reduction.
During the 36-week open-label lead-in, participants lost an average of 20.9% of their body weight on tirzepatide. After randomization, those who continued treatment lost an additional 5.5%, while those who switched to placebo regained 14.0% from their week-36 weight. A striking 89.5% of participants staying on tirzepatide kept at least 80% of their initial weight loss, compared to just 16.6% in the placebo group.
Key Numbers
n=670 · 20.9% weight loss at 36 weeks · 25.3% total loss with continued treatment at 88 weeks · 9.9% total loss with placebo · 89.5% maintained ≥80% of weight loss on tirzepatide vs 16.6% on placebo · P<.001
How They Did This
Phase 3, randomized withdrawal design at 70 sites across 4 countries. Adults with BMI ≥30 (or ≥27 with a weight-related condition) but without diabetes received open-label tirzepatide at the maximum tolerated dose (10 or 15 mg weekly, subcutaneous) for 36 weeks. At week 36, 670 participants were randomized 1:1 to either continue tirzepatide or switch to placebo for an additional 52 weeks (through week 88). Double-blind during the randomized period.
Why This Research Matters
This trial answers a critical question in obesity medicine: what happens when you stop taking tirzepatide? The answer is clear — most of the weight comes back. This has major implications for patients and healthcare systems, because it suggests tirzepatide works best as a long-term or indefinite treatment rather than a short course. The results also demonstrate that continuing treatment doesn't just maintain weight loss but actually deepens it, with participants losing an additional 5.5% beyond what they achieved in the first 36 weeks.
The Bigger Picture
The SURMOUNT-4 results join a growing body of evidence showing that obesity medications, including GLP-1 receptor agonists, often need to be taken long-term to maintain results. This parallels findings with semaglutide (the STEP trials) and has significant implications for insurance coverage, healthcare costs, and how we think about obesity as a chronic condition requiring ongoing treatment rather than a problem with a one-time fix.
What This Study Doesn't Tell Us
The trial excluded people with diabetes, so results may not generalize to that population. The randomized withdrawal design means all participants received tirzepatide initially — there's no pure placebo control from baseline. The study population was mostly women (71%) and the mean age was 48 years. Long-term safety and weight outcomes beyond 88 weeks remain unknown. The trial was industry-sponsored by Eli Lilly.
Questions This Raises
- ?Is there an optimal duration of treatment after which some patients can safely taper off tirzepatide without full weight regain?
- ?Would adding exercise or behavioral interventions help maintain weight loss after stopping the medication?
- ?How do these results apply to people with type 2 diabetes or other metabolic conditions?
Trust & Context
- Key Stat:
- 25.3% total weight loss Participants who continued tirzepatide for 88 weeks achieved this reduction from their starting weight, compared to 9.9% in those who stopped at 36 weeks.
- Evidence Grade:
- This is a large, phase 3, double-blind, placebo-controlled randomized clinical trial published in JAMA — one of the highest-impact medical journals. The sample size (670 randomized participants) provides strong statistical power, and the randomized withdrawal design directly answers the clinical question of treatment continuation.
- Study Age:
- Published in 2024, this study reflects very recent evidence on tirzepatide's weight maintenance effects and remains highly relevant to current clinical practice.
- Original Title:
- Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.
- Published In:
- JAMA, 331(1), 38-48 (2024)
- Authors:
- Aronne, Louis J(7), Sattar, Naveed(10), Horn, Deborah B(3), Bays, Harold E, Wharton, Sean, Lin, Wen-Yuan, Ahmad, Nadia N, Zhang, Shuyu, Liao, Ran, Bunck, Mathijs C, Jouravskaya, Irina, Murphy, Madhumita A
- Database ID:
- RPEP-07771
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
How much weight did people regain after stopping tirzepatide?
Participants who switched to placebo at week 36 regained an average of 14 percentage points of their body weight over the next 52 weeks. They had lost 20.9% during treatment but ended at only 9.9% total loss from baseline — meaning they regained more than half of what they'd lost.
Does tirzepatide keep working after the initial weight loss period?
Yes. Participants who continued treatment didn't just maintain their 20.9% weight loss — they lost an additional 5.5%, bringing their total to 25.3% at 88 weeks. This suggests the drug's weight-reducing effects continue well beyond the first several months.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-07771APA
Aronne, Louis J; Sattar, Naveed; Horn, Deborah B; Bays, Harold E; Wharton, Sean; Lin, Wen-Yuan; Ahmad, Nadia N; Zhang, Shuyu; Liao, Ran; Bunck, Mathijs C; Jouravskaya, Irina; Murphy, Madhumita A. (2024). Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.. JAMA, 331(1), 38-48. https://doi.org/10.1001/jama.2023.24945
MLA
Aronne, Louis J, et al. "Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.." JAMA, 2024. https://doi.org/10.1001/jama.2023.24945
RethinkPeptides
RethinkPeptides Research Database. "Continued Treatment With Tirzepatide for Maintenance of Weig..." RPEP-07771. Retrieved from https://rethinkpeptides.com/research/aronne-2024-continued-treatment-with-tirzepatide
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.