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Secondary analysis of a randomized trial

SURMOUNT-1 body composition: fat vs lean mass on tirzepatide

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 (p < 0.001 for all comparisons).

Look M et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes, Obesity and Metabolism, 2025. DOI: 10.1111/dom.16275

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Key facts

Drug
tirzepatide
Design
Secondary analysis of a randomized trial
Participants
160
Duration
72 weeks
Funding
Eli Lilly
Registry
NCT04184622
Population
160 of the 2,539 SURMOUNT-1 participants with a DXA scan at baseline and at week 72 (124 on tirzepatide, doses pooled, and 36 on placebo); 73% women, mean weight 102.5 kg and mean BMI 38.0, without diabetes.
Primary outcome
Change in weight, fat mass and lean mass measured by DXA from baseline to week 72, overall and, post hoc, by sex, age and tertile of weight loss.

What it found

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 (p < 0.001 for all comparisons). Of the weight lost, about 75% was fat mass and 25% lean mass, with both tirzepatide and placebo. These proportions held in most subgroups by sex, age and amount of weight lost.

This is a secondary analysis: it uses data from a trial that was already published, so its conclusions carry less weight than that trial’s main result.

Limitations

The trial was funded by Eli Lilly. A small substudy, with only 36 participants in the placebo group and the tirzepatide doses pooled. The subgroup analyses were post hoc. Lean mass measured by DXA includes organs, water and other tissues besides muscle.

What it means for you

With tirzepatide, about three quarters of the weight lost was fat and a quarter was lean mass, the same proportion as with placebo. The lean mass measured by a DXA scan is not just muscle. If you are worried about losing muscle, physical activity and diet are topics to discuss with your doctor or a registered dietitian.

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.

  • 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.

  • 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. Diabetes, Obesity and Metabolism.Look M, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025;27(5):2720-2729.accessed .
  2. Europe PMC.Europe PMC record PMID 39996356 (abstract; PMC11965027).accessed .