The sentence in the US labels
In section 12.2, the Zepbound® label states that tirzepatide reduces body weight, with fat mass falling by more than lean mass [1]. The Wegovy® label says the same of semaglutide, the Foundayo™ label of orforglipron, and the Canadian Zepbound® monograph repeats it in its own pharmacodynamics section [2][3][12].
Two things are worth noticing. The sentence compares the two parts: more fat than lean, not no lean at all. And none of these documents gives a percentage or a number of kilograms for either part.
The sentence is not universal. The Saxenda® label says liraglutide lowers weight through lower calorie intake and does not raise 24-hour energy use, and makes no statement about fat and lean mass [4].
What the European product information adds
In Europe, Mounjaro® is the tirzepatide brand for weight management as well as diabetes. Its section 5.1 describes a body-composition sub-study of SURMOUNT-1, the trial the Zepbound® label calls Study 1, using dual-energy X-ray absorptiometry (DEXA), a type of body scan. After 72 weeks, fat mass had fallen more than lean body mass compared with placebo, visceral fat had fallen with total fat, and the document concludes that most of the weight lost was fat tissue [5].
The European Wegovy® document describes two semaglutide sub-studies: DEXA in 140 people from STEP 1 after 68 weeks, and magnetic resonance imaging in 55 people from STEP UP after 72 weeks, which tested 2.4 mg and 7.2 mg. Both found more fat than lean mass lost compared with placebo, with less visceral fat in STEP 1 [6]. Neither document prints the lean mass figures.
The tirzepatide body-scan numbers
The SURMOUNT-1 sub-study was published in 2025. Of the trial’s 2,539 participants [9], 160 had DEXA scans at the start and at week 72: 124 on any tirzepatide dose and 36 on placebo, 73% of them women [7].
With tirzepatide, body weight fell by 21.3%, fat mass by 33.9% and lean mass by 10.9%. With placebo the falls were 5.3%, 8.2% and 2.6%. In both groups, about 75% of the weight lost was fat and about 25% lean mass, and post hoc subgroup analyses by sex, by age (under 50, 50 to 64, 65 and over) and by amount of weight lost found the proportions broadly the same [7].
Read it with its limits. It is a sub-study of a few percent of the trial, the subgroup analyses were not planned in advance, and most of its authors are employees of the manufacturer. A 2025 correction changed only an axis label on one figure, not the results [7]. The figures describe tirzepatide in this trial; they are not a benchmark for other medicines.
What “lean mass” counts, and why figures differ
Lean mass is everything a scan does not class as fat. A 2024 review notes that it includes organs, bone, fluids and the water inside fat tissue, so a fall in lean mass is not the same as an equal fall in muscle [8].
The same review found wide variation between GLP-1 studies: in some, lean mass made up 40% to 60% of the weight lost, in others about 15% or less. It points to differences in who was studied, which medicine, and other illnesses. From newer MRI studies it suggests that muscle changes on these medicines are largely in line with age, disease and the amount of weight lost, and that muscle quality may improve. It also flags older age and more severe disease as reasons for extra care about muscle loss [8].
Strength and function: what was and was not measured
The labels do not report muscle strength. What the European documents report is questionnaire-based physical functioning: small improvements with semaglutide, and with tirzepatide small improvements that were greater than with placebo [5][6]. The STEP 1 abstract likewise describes a larger rise in participant-reported physical functioning with semaglutide than with placebo [10].
The review’s main research call is for exactly this gap to be filled: better measures of muscle mass and composition alongside function, mobility and strength [8].
Exercise alongside a GLP-1: one trial’s body-fat result
No label tests whether training or protein shifts the fat-to-lean balance. One randomised trial, S-LITE, gives a partial view: after a diet, adults spent a year on liraglutide, supervised exercise, both, or placebo. Body-fat percentage fell by 3.9 points with the combination, roughly double the fall seen with exercise or liraglutide on its own [13]. It measured body-fat percentage, not muscle, and used liraglutide only; the article on exercise covers the trial in full.
The weight-management trials in the labels counselled everyone to be more active, aiming for at least 150 minutes each week [1]. The NIDDK cites the federal activity guidelines, which add muscle-strengthening work twice or more each week [11]. Which kind suits you is a question for your clinician.
Questions for your clinician
- Given my age and health, is the pace of my weight loss something to watch for muscle?
- Which strength activities are safe for me, and how often?
- With my appetite this low, should someone review how much protein and food I am getting?
- Would a body composition scan be useful for me, and what would we do with the result?
An open research question
The NIDDK lists, among future approaches researchers are exploring for weight-management medicines, helping people lose body fat without losing muscle [11]. Keeping lean tissue during weight loss is still a research goal, and new medicines aimed at muscle are in development alongside GLP-1 treatment [8].
Zepbound® and Mounjaro® are registered trademarks and Foundayo™ is a trademark of Eli Lilly and Company. Wegovy® and Saxenda® are registered trademarks of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by Eli Lilly and Company or Novo Nordisk.
When to get help
| Sign | Who to contact | How fast | Source |
|---|---|---|---|
| You are 65 or older, already frail, or have a long-term illness, and are starting or on a GLP-1 | Your prescriber, about muscle health | At your next appointment | Review of lean mass on GLP-1-based therapies [8] |
| Dizziness or fainting, especially when standing or with vomiting or diarrhea | Your prescriber | Today | Wegovy® label 6.1 and Medication Guide; Zepbound® label 6.1 [2][1] |
| Nausea, vomiting or diarrhea that does not settle | Your prescriber | Today | Wegovy® Medication Guide [2] |
