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Randomized controlled trial

SURMOUNT-4: what happens after stopping tirzepatide (Zepbound)

From week 36 to week 88, weight changed by −5.5% in those who stayed on tirzepatide and by +14.0% in those switched to placebo (difference of −19.4 percentage points; 95% CI, −21.2 to −17.7).

Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA, 2024. DOI: 10.1001/jama.2023.24945

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Key facts

Drug
tirzepatide
Design
Randomized controlled trial
Participants
670
Duration
88 weeks
Funding
Eli Lilly
Registry
NCT04660643
Population
783 adults with a BMI of 30 or more (or 27 or more with at least one weight-related complication), without diabetes, at 70 sites in 4 countries; 670 were randomized after 36 weeks of open-label treatment (mean age 48 years, 71% women, mean weight 107.3 kg).
Primary outcome
Mean percentage change in weight from week 36 (randomization) to week 88, continuing tirzepatide versus switching to placebo.

What it found

From week 36 to week 88, weight changed by −5.5% in those who stayed on tirzepatide and by +14.0% in those switched to placebo (difference of −19.4 percentage points; 95% CI, −21.2 to −17.7). Before randomization, during the first 36 weeks on the maximum tolerated dose of tirzepatide (10 or 15 mg), they had lost an average of 20.9% of their weight. Of those who continued, 89.5% kept off at least 80% of the weight they had lost, compared with 16.6% on placebo. From week 0 to week 88, the mean reduction was 25.3% with tirzepatide and 9.9% with placebo. The most common adverse effects were digestive, mostly mild or moderate, and more frequent with tirzepatide.

Limitations

Funded by Eli Lilly, which took part in the design, analysis and writing. The initial 36-week open-label period selected people who tolerated the drug. People with diabetes were excluded. It reflects complete withdrawal to placebo, not a gradual dose reduction or a switch to another treatment, and it did not evaluate specific nutrition strategies after withdrawal.

What it means for you

People switched from tirzepatide to placebo regained a good part of the weight within a year, while those who stayed on the drug kept losing. This is key if you are wondering what happens when treatment stops. The decision to continue or stop is one for your doctor, who can assess your case.

Further reading

Related trials

  • tirzepatide112 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.

  • tirzepatide72 weeks

    SURMOUNT-1 (body composition)

    At 72 weeks, weight changed by −21.3%, fat mass by −33.9% and lean mass by −10.9% with tirzepatide, compared with −5.3%, −8.2% and −2.6% on placebo.

  • tirzepatide and semaglutide72 weeks

    SURMOUNT-5

    At 72 weeks, weight fell by 20.2% with tirzepatide and 13.7% with semaglutide.

  • tirzepatide52 weeks

    SURMOUNT-OSA

    At 52 weeks, the AHI fell by 25.3 events per hour with tirzepatide and 5.3 with placebo in trial 1, and by 29.3 versus 5.5 in trial 2.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. JAMA.Aronne LJ, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38-48.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 38078870 (abstract).accessed .
  3. PubMed Central (National Library of Medicine).Full text PMC10714284 (funding).accessed .