SURMOUNT-1 scan substudy finds tirzepatide weight loss is about 75% fat and 25% lean mass

About three-quarters of the weight lost by people taking tirzepatide in a substudy of the SURMOUNT-1 trial came from fat, and about one-quarter came from lean tissue, according to results published February 25, 2025, in the journal Diabetes, Obesity and Metabolism ^[2][4].

Researchers scanned 160 of the 2,539 SURMOUNT-1 participants with dual-energy X-ray absorptiometry, or DXA, at the start of the study and again at week 72 ^[4]. Of those 160 people, 124 received pooled tirzepatide doses of 5, 10 or 15 mg and 36 received placebo. The group was 73% female, with a mean weight of 102.5 kg and a mean body mass index of 38.0 ^[4].

Over 72 weeks, body weight fell 21.3%, fat mass fell 33.9% and lean mass fell 10.9% in the tirzepatide group. In the placebo group, the same three measures fell 5.3%, 8.2% and 2.6%. All differences between the groups were statistically significant, with p values below 0.001 ^[4].

The 75% fat, 25% lean split was the same in both groups, and the authors report it held across most of the subgroups they examined: by sex, by age (under 50, 50 to under 65, and 65 and older), and by how much weight each participant lost (groups of 15.3 kg or less, more than 15.3 to 25.9 kg, and more than 25.9 kg) ^[4]. Those subgroup analyses were done after the fact, which the authors describe as post hoc ^[4].

The paper notes that DXA lean mass is not the same as muscle alone; it is total fat-free mass minus bone mineral content. The authors write that losing too much lean mass, particularly skeletal muscle, may reduce physical function, muscle strength, resting energy expenditure and neuromuscular function, and may increase fatigue and injury risk ^[4]. They also note that many studies of dietary restriction report roughly the same 75/25 split ^[4].

Tirzepatide is a once-weekly drug that activates the GIP and GLP-1 receptors. It is approved for adults with obesity or overweight plus a weight-related condition such as hypertension, high cholesterol, obstructive sleep apnea or cardiovascular disease, and for adults with type 2 diabetes ^[4]. In the main SURMOUNT-1 trial, mean weight change at 72 weeks was -16.0% at 5 mg, -21.4% at 10 mg and -22.5% at 15 mg, compared with -2.4% for placebo ^[4].

Several authors are employees and shareholders of Eli Lilly and Company, and the paper's copyright line names the company ^[1][4]. Two academic authors report consulting or speaking fees from Eli Lilly, Novo Nordisk and other companies ^[1]. A correction notice for the paper was later published in the same journal ^[1][4].

Why it matters for patients

People starting or considering these medications often hear that they cause muscle loss. This substudy puts a number on that: lean mass did fall 10.9% over 72 weeks on tirzepatide, but it also fell 2.6% on placebo, and the share of total weight lost as lean tissue was the same in both groups ^[4]. In this group of participants, the drug did not appear to change the fat-to-lean ratio of weight loss, which looked like the ratio typically seen with dieting ^[4].

Several practical questions are not answered here. The report does not describe whether participants did resistance training or how much protein they ate, and it does not report whether the lean mass changes affected strength, walking speed or day-to-day function. It also does not say whether lean mass came back later, since there was no follow-up scan after week 72. The substudy covered 160 people in a trial that enrolled 2,539, and it was 73% female, so results in the full trial population could differ ^[4].