Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight

Michelle Look; Julia P Dunn; Robert F Kushner; Dachuang Cao; Charles Harris; Theresa Hunter Gibble; Adam Stefanski; Ryan Griffin

doi:10.1111/dom.16275

Therapeutics Metabolic and Endocrine Agents

Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight

Look M, Dunn JP, Kushner RF, Cao D, Harris C, Gibble TH, Stefanski A, Griffin R

Published May 2025 Diabetes, Obesity and Metabolism

DOI 10.1111/dom.16275 PMID 39996356 PMC PMC11965027

RRM Academy Synopsis

Tirzepatide weight loss was about 75% fat and 25% lean mass

In a placebo-controlled substudy of 160 adults with obesity or overweight, tirzepatide weight loss was about 75% fat mass and 25% lean mass, a split similar to placebo. Body weight fell 21.3% with tirzepatide and 5.3% with placebo over 72 weeks.

Key Findings

Body weight changed by −21.3% with tirzepatide and −5.3% with placebo at Week 72 (estimated treatment difference −16.0; 95% confidence interval [CI]: −19.4, −12.6).
Fat mass changed by −33.9% with tirzepatide and −8.2% with placebo. Lean mass changed by −10.9% and −2.6% in the same two groups. Each of these comparisons had p < 0.001.
Of the weight lost on tirzepatide, 74% came from fat mass and 26% from lean mass. In the placebo group, fat mass made up 75% and lean mass 25%.
Visceral fat mass changed by −40.1% with tirzepatide and −7.3% with placebo. Waist circumference fell 18.1 cm on tirzepatide and 3.4 cm on placebo.
With tirzepatide, the fat share was 74%, 75% and 76% across the three age groups. Two subgroups differed: placebo participants aged ≥65 years (63%) and the lowest weight-reduction tertile (70%).

Interpretation

The report is a substudy of a randomized, double-blind, placebo-controlled trial. Dual-energy X-ray absorptiometry (DXA) scans measured body composition at baseline and Week 72 in 160 of the 2539 participants. The adults had obesity or overweight, had no type 2 diabetes, and received lifestyle counseling. The subgroup analyses by sex, age and weight-reduction tertile were post hoc. The authors state that the subgroups were small and that nominal differences between them should not drive conclusions. Eli Lilly and Company funded the work, and several authors work for the company.

RRM Context

Restorative reproductive medicine treats metabolic health as part of the root cause of cycle and fertility problems in both partners. Fat and lean tissue measures describe metabolic health more fully than body weight alone. Women made up 73% of the 160 participants in this substudy.

Our editorial summary of this paper, not the article's abstract.

Abstract

Aims

We assessed changes in body composition following tirzepatide treatment in a substudy of participants with obesity or overweight from the SURMOUNT-1 trial, overall and post hoc in clinically relevant subgroups.

Materials and Methods

Substudy participants (n = 160 of the 2539 in SURMOUNT-1) underwent dual-energy X-ray absorptiometry (DXA) at baseline and Week 72. Body composition parameters were evaluated by analysis of covariance, logistic regression or Fisher's exact test. Post hoc subgroup analyses were conducted by sex (female or male), age (<50, 50 to <65, or ≥65 years) and total body weight reduction tertiles (≤15.3 kg, >15.3 to ≤25.9 kg, or >25.9 kg).

Results

The 160 participants (pooled tirzepatide doses n = 124, placebo n = 36) with baseline and end of study DXA data were 73% female and had a mean weight of 102.5 kg and body mass index of 38.0 kg/m2. The change in body weight, fat mass and lean mass from baseline to Week 72 was -21.3%, -33.9% and -10.9% with tirzepatide and -5.3%, -8.2% and -2.6% with placebo, respectively (p < 0.001 for all comparisons). Of the body weight lost, approximately 75% was fat mass and 25% was lean mass for both tirzepatide and placebo. These proportions remained consistent across most subgroup analyses.

Conclusions

In participants with obesity or overweight from the SURMOUNT-1 trial, tirzepatide treatment significantly reduced body weight, fat mass and lean mass compared with placebo, while in post hoc analyses, the proportion of body weight lost as fat or lean mass was relatively consistent including in clinically relevant subgroups.

Topics

Therapeutics

Metabolic and Endocrine Agents GLP-1 Receptor Agonists

Therapeutics › Metabolic and Endocrine Agents › GLP-1 Receptor Agonists

Michelle Look, Julia P Dunn, Robert F Kushner, Dachuang Cao, Charles Harris, Theresa Hunter Gibble, Adam Stefanski, Ryan Griffin

M Look, J Dunn, Bob Kushner, Rob Kushner, Bobby Kushner, R Kushner, D Cao, Charlie Harris, Chuck Harris, C Harris, T Gibble, A Stefanski, R Griffin

PMID 39996356 39996356 DOI 10.1111/dom.16275 10.1111/dom.16275 Look et al. 2025, Look 2025

Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight

Tirzepatide weight loss was about 75% fat and 25% lean mass

Key Findings

Interpretation

RRM Context

Abstract

Topics

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