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Randomized controlled trial

SURMOUNT-5: tirzepatide vs semaglutide (Zepbound vs Wegovy)

At 72 weeks, weight fell by 20.2% with tirzepatide (95% CI, −21.4 to −19.1) and 13.7% with semaglutide (95% CI, −14.9 to −12.6); the estimated difference was −6.5 percentage points (95% CI, −8.1 to −4.9; p < 0.001).

Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. New England Journal of Medicine, 2025. DOI: 10.1056/NEJMoa2416394

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Key facts

Drugs
tirzepatide and semaglutide
Design
Randomized controlled trial
Participants
751
Duration
72 weeks
Funding
Eli Lilly
Registry
NCT05822830
Population
751 adults with obesity (or overweight with at least one weight-related complication), without diabetes.
Primary outcome
Percentage change in body weight at 72 weeks with tirzepatide (maximum tolerated dose of 10 or 15 mg) versus semaglutide (maximum tolerated dose of 1.7 or 2.4 mg).

What it found

Mean weight loss, % of starting weight · 72 weeks
  • Tirzepatide 10 or 15 mg (maximum tolerated)95% CI, −21.4 to −19.1−20.2%
  • Semaglutide 1.7 or 2.4 mg (maximum tolerated)95% CI, −14.9 to −12.6−13.7%

Difference: −6.5 points with tirzepatide vs semaglutide (95% CI, −8.1 to −4.9).

See the results in a chart

At 72 weeks, weight fell by 20.2% with tirzepatide (95% CI, −21.4 to −19.1) and 13.7% with semaglutide (95% CI, −14.9 to −12.6); the estimated difference was −6.5 percentage points (95% CI, −8.1 to −4.9; p < 0.001). It is the first head-to-head comparison of the two drugs in obesity. Waist circumference decreased by 18.4 cm versus 13.0 cm. The most common adverse effects were digestive in both groups.

Limitations

Funded by Eli Lilly, the maker of tirzepatide. Open-label design (participants knew which drug they were getting), which can influence adherence and the effects reported. No placebo group.

What it means for you

In the first head-to-head comparison in obesity, tirzepatide (Zepbound) reduced weight by 6.5 percentage points more than semaglutide (Wegovy) over 72 weeks. It was an open-label trial funded by the maker of tirzepatide. An average difference does not tell you which drug will work better for a given person; that is for the doctor to assess.

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.

  • 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.

  • 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. New England Journal of Medicine.Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26-36.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 40353578 (abstract).accessed .