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Randomized controlled trial

SURMOUNT-1: tirzepatide (Zepbound) for obesity without diabetes

At 72 weeks, the mean change in weight was −15.0% with tirzepatide 5 mg (95% CI, −15.9 to −14.2), −19.5% with 10 mg (95% CI, −20.4 to −18.5) and −20.9% with 15 mg (95% CI, −21.8 to −19.9), compared with −3.1% on placebo (95% CI, −4.3 to −1.9).

Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 2022. DOI: 10.1056/NEJMoa2206038

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Key facts

Drug
tirzepatide
Design
Randomized controlled trial
Participants
2,539
Duration
72 weeks
Funding
Eli Lilly
Registry
NCT04184622
Population
2,539 adults with a BMI of 30 or more (or 27 or more with at least one weight-related complication), without diabetes; mean starting weight of 104.8 kg.
Primary outcome
Percentage change in body weight and proportion losing at least 5% at 72 weeks, for each tirzepatide dose versus placebo.

What it found

Mean weight loss, % of starting weight · 72 weeks
  • Tirzepatide 5 mg weekly95% CI, −15.9 to −14.2−15.0%
  • Tirzepatide 10 mg weekly95% CI, −20.4 to −18.5−19.5%
  • Tirzepatide 15 mg weekly95% CI, −21.8 to −19.9−20.9%
  • Placebo95% CI, −4.3 to −1.9−3.1%

Difference (Tirzepatide 5 mg weekly): −11.9 points vs placebo (subtraction).

Difference (Tirzepatide 10 mg weekly): −16.4 points vs placebo (subtraction).

Difference (Tirzepatide 15 mg weekly): −17.8 points vs placebo (subtraction).

Figures from the paperSee the results in a chart

At 72 weeks, the mean change in weight was −15.0% with tirzepatide 5 mg (95% CI, −15.9 to −14.2), −19.5% with 10 mg (95% CI, −20.4 to −18.5) and −20.9% with 15 mg (95% CI, −21.8 to −19.9), compared with −3.1% on placebo (95% CI, −4.3 to −1.9). At least 5% of body weight was lost by 85%, 89% and 91% of participants on 5, 10 and 15 mg, compared with 35% on placebo. On 10 and 15 mg, 50% and 57% lost at least 20% of their weight, compared with 3% on placebo. The most common adverse effects were digestive, mostly mild or moderate and concentrated in the dose-escalation phase; they led 4.3%, 7.1% and 6.2% of participants on tirzepatide and 2.6% on placebo to stop treatment.

Limitations

Funded by Eli Lilly. People with diabetes were excluded. It did not compare tirzepatide directly with semaglutide (SURMOUNT-5 did). The results reflect continued treatment with lifestyle support.

What it means for you

SURMOUNT-1 is the benchmark for weight loss with tirzepatide (Zepbound) in people with obesity without diabetes: an average of 15.0% to 20.9% depending on the dose, over 72 weeks. These are averages from a closely monitored trial, and individual responses vary a lot. The right dose for each person is decided by their 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. New England Journal of Medicine.Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 35658024 (abstract).accessed .