tirzepatide · 112 weeks
SURMOUNT-MAINTAIN
At week 112, weight had changed by −21.9% on the maximum tolerated dose of tirzepatide, −16.6% on 5 mg and −9.9% on placebo.
Secondary analysis of a randomized trial
SURMOUNT-4 post hoc: weight regain and cardiometabolic health
After switching from tirzepatide to placebo, the more weight people regained between week 36 and week 88, the more their cardiometabolic parameters worsened: waist circumference increased by 0.8 cm (95% CI, −1.0 to 2.6) in those who regained less than 25% of the weight lost and by 14.7 cm (95% CI, 12.7 to 16.7) in those who regained 75% or more.
Horn DB et al. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Internal Medicine, 2026. DOI: 10.1001/jamainternmed.2025.6112
- Prepared by
- Alex Gonzalez
- Last updated
- Sources
- 3 sources
No clinical review. No advertising from drug companies and no affiliate links.How we work
Key facts
- Drug
- tirzepatide
- Design
- Secondary analysis of a randomized trial
- Participants
- 308
- Duration
- 88 weeks
- Funding
- Eli Lilly
- Registry
- NCT04660643
- Population
- 308 SURMOUNT-4 participants who lost at least 10% of their weight during the first 36 weeks on tirzepatide and were randomized to placebo (71.1% women, mean age 47.1 years).
- Primary outcome
- Changes in cardiometabolic parameters between week 36 and week 88 according to the share of lost weight regained after tirzepatide was withdrawn (less than 25%, 25 to 50%, 50 to 75% and 75% or more).
What it found
After switching from tirzepatide to placebo, the more weight people regained between week 36 and week 88, the more their cardiometabolic parameters worsened: waist circumference increased by 0.8 cm (95% CI, −1.0 to 2.6) in those who regained less than 25% of the weight lost and by 14.7 cm (95% CI, 12.7 to 16.7) in those who regained 75% or more. Of the 308 participants, 54 regained less than 25%, 77 between 25 and 50%, 103 between 50 and 75% and 74 regained 75% or more. Systolic blood pressure rose in all groups, from 6.8 mm Hg (95% CI, 3.9 to 9.7) in the lowest-regain group to 10.4 mm Hg (95% CI, 8.0 to 12.8) in the highest, and HbA1c rose by 0.14 to 0.35 points. In those who regained less than 25%, waist circumference, non-HDL cholesterol and fasting insulin did not change significantly from week 36.
Limitations
Funded by Eli Lilly, with several authors employed by the company. Post hoc analysis: the regain categories were not randomized and do not allow conclusions about cause and effect. It only includes people who lost at least 10% and excluded people with diabetes.
What it means for you
This analysis suggests that improvements in waist size, blood pressure or blood sugar fade as weight comes back after stopping tirzepatide. It is a later analysis that does not prove cause and effect. If you are thinking about stopping treatment, these figures are useful for talking with your doctor about how to monitor your health.
Further reading
- How Much Weight Do People Lose on Ozempic, Wegovy or Zepbound? Trial Data
- Ozempic vs Mounjaro (and Zepbound): Real Differences From the Trials and Labels
- What Happens When You Stop Ozempic, Wegovy or Zepbound: Weight Regain, Explained
- GLP-1 drug pages
- All study summaries
- Original paper: doi.org/10.1001/jamainternmed.2025.6112
Sources
The original paper and the records consulted for this summary, with the date they were accessed.
- JAMA Internal Medicine.Horn DB, et al. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Intern Med. 2026;186(2):157-167.accessed .
- National Library of Medicine (PubMed).PubMed record PMID 41284285 (abstract).accessed .
- PubMed Central (National Library of Medicine).Full text PMC12645400 (funding).accessed .