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Randomized controlled trial

SURMOUNT-3: tirzepatide (Zepbound) after a lifestyle program

From randomization to week 72, weight changed by an additional −18.4% with tirzepatide and +2.5% with placebo; the estimated difference was −20.8 percentage points (95% CI, −23.2 to −18.5).

Wadden TA et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine, 2023. DOI: 10.1038/s41591-023-02597-w

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Key facts

Drug
tirzepatide
Design
Randomized controlled trial
Participants
579
Duration
72 weeks
Funding
Eli Lilly
Registry
NCT04657016
Population
806 adults with a BMI of 30 or more (or 27 or more with at least one obesity-related complication), without diabetes, started a 12-week intensive lifestyle intervention. The 579 who lost at least 5.0% of their weight (6.9% on average, from 109.5 to 101.9 kg) were randomized to tirzepatide, 287, or to placebo, 292; 62.9% women and mean age 45.6 years.
Primary outcome
Two co-primary objectives from randomization to week 72: additional percentage change in weight and proportion of participants who lost at least an additional 5%, with the maximum tolerated dose of tirzepatide (10 or 15 mg once weekly) versus placebo.

What it found

Mean weight loss, % of starting weight · 72 weeks
  • Tirzepatide 10 or 15 mg (maximum tolerated)−18.4%
  • Placebo+2.5%

Difference: −20.8 points vs placebo (95% CI, −23.2 to −18.5).

Figures from the paperSee the results in a chart

From randomization to week 72, weight changed by an additional −18.4% with tirzepatide and +2.5% with placebo; the estimated difference was −20.8 percentage points (95% CI, −23.2 to −18.5). Of those on tirzepatide, 87.5% lost at least an additional 5%, compared with 16.5% on placebo (OR 34.6; 95% CI, 19.2 to 62.6). These are results for the treatment-regimen estimand, which includes everyone randomized whether or not they stayed on treatment; with the efficacy estimand, which assumes everyone stayed on it, the difference was −24.5 percentage points (95% CI, −26.1 to −22.8). The most common adverse effects with tirzepatide were digestive, mostly mild or moderate; 10.5% stopped treatment because of adverse effects, compared with 2.1% on placebo.

Limitations

Funded by Eli Lilly, which contributed to the design, oversaw the conduct of the study and supported the writing. It only included people who had already lost at least 5.0% of their weight in the initial 12-week phase, a selected group. People with diabetes were excluded, and most participants were white (86.0%). More participants completed the study on tirzepatide than on placebo (87.8% versus 77.7%).

What it means for you

People who had already lost weight on an intensive lifestyle program lost an additional 18.4% on tirzepatide (Zepbound) over 72 weeks, while those on placebo regained some weight. It suggests the drug can be added to lifestyle changes, not replace them. If you have already lost weight on your own and are considering treatment, it is a topic to discuss with your doctor.

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.

  • tirzepatide88 weeks

    SURMOUNT-4

    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.

Sources

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

  1. Nature Medicine.Wadden TA, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909-2918.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 37840095 (abstract).accessed .
  3. PubMed Central (National Library of Medicine).Full text PMC10667099 (lead-in, efficacy estimand, discontinuations and funding).accessed .