Does Retatrutide Cause Muscle Loss? The Short Answer

Some, yes, as with other weight-loss treatments. In the only published DXA study of retatrutide, total fat mass fell by up to 26.1% over 36 weeks and lean mass, which includes muscle, by up to 6.5 kg (about 14 lb). The authors reported that the proportion of lean mass loss to weight loss was similar to other obesity treatments; a medical-news summary of the full paper puts fat at 62% to 69% of the weight lost at the effective doses, which would make roughly a third lean mass.

For comparison, in body composition substudies of the approved drugs, lean mass made up about a quarter of the weight lost with tirzepatide and about two fifths with semaglutide (evidence: separate trials with different populations and lengths, so not a direct comparison).

The retatrutide study was small, lasted 36 weeks and enrolled people with type 2 diabetes. TRIUMPH-1, a Phase 3 obesity trial published in full in September 2026, did not report body composition in its main paper, so how much muscle people lose with the larger weight loss seen in those trials is not yet known.

The Body Composition Study

The evidence comes from a substudy of a Phase 2 trial in adults with type 2 diabetes, published in The Lancet Diabetes & Endocrinology (online June 2025, August 2025 issue) (Coskun et al.) and funded by the drug's developer. Participants received retatrutide at doses from 0.5 mg to 12 mg, dulaglutide (an approved GLP-1 medicine) or placebo for 36 weeks, at 42 US centers.

Body composition was measured with dual-energy X-ray absorptiometry (DXA), which separates fat mass from lean mass. Of 189 people enrolled in the substudy, 103 completed treatment with scans at both the start and week 36. The prespecified main outcome was the percent change in total fat mass.

The 4 mg and 8 mg figures pool groups that started at different doses. Lean mass fell by up to 6.5 kg. According to a medical-news summary of the full paper, lean mass fell by up to 12.5% (8 mg) and the "fat loss index", the share of total weight lost that was fat, ranged from 62.0% to 69.3% across the effective doses; those two figures are not in the abstract. Fat mass fell more with retatrutide 4 mg and above than with dulaglutide or placebo, and the authors concluded that retatrutide "significantly improved total body fat mass reduction compared with placebo and dulaglutide."

What the Study Says About Lean Mass

The authors concluded that retatrutide produced greater weight loss than other drugs "without inducing proportionally more loss of lean mass," and that its fat loss index "was consistent with most other weight loss treatments." If the summary figures above are right, about two thirds of the weight lost was fat and about one third was lean mass.

For context, the approved drugs have their own body composition substudies. In SURMOUNT-1, tirzepatide reduced fat mass by about 34% and lean mass by about 11%, so roughly three quarters of the weight lost was fat. In STEP 1, about 40% of the weight lost with semaglutide was lean mass. These were separate trials in people without diabetes, over 72 and 68 weeks, so the figures show the typical range rather than which drug preserves more muscle.

Two other points limit what this study can tell us:

• Lean mass is not the same as muscle. DXA lean mass also includes water, organs and other non-fat tissue, so it is an indirect measure of muscle.
• The population was different. The participants had type 2 diabetes and were treated for 36 weeks. People without diabetes in TRIUMPH-1 lost more weight over a longer period, and their body composition may have changed differently.

What the Phase 3 Trials Report

The main text of the TRIUMPH-1 paper, published in the New England Journal of Medicine in September 2026, does not report body composition, and neither does the 2023 Phase 2 obesity trial paper. TRIUMPH-1 did report that physical function, measured with a quality-of-life questionnaire (SF-36v2), improved more with retatrutide than with placebo, which is a measure of how people felt they could function rather than of muscle mass.

The TRIUMPH-1 protocol allowed dose reductions for excessive weight loss or a BMI of 22 or less, and some participants stopped treatment because of perceived excessive or sufficient weight loss: 5.3% with 12 mg, 1.0% with 9 mg and 0.3% with 4 mg, compared with none on placebo.

Does the Glucagon Component Matter?

Retatrutide differs from semaglutide and tirzepatide by also activating the glucagon receptor, and it is sometimes claimed that this either protects or harms muscle. Neither claim has been tested. The body composition study did not compare retatrutide with tirzepatide or semaglutide, and no published retatrutide trial was designed to separate the effect of each receptor on muscle.

What Is Still Unknown

• How much lean mass and muscle people lose with retatrutide in the Phase 3 trials.
• Whether lean mass changes differ by dose, sex or age.
• Whether retatrutide affects muscle strength or physical performance, measured directly.
• Whether diet or exercise programs change body composition on retatrutide; the trials described here did not test them.
• What happens to lean mass after stopping; that is covered in weight regain after stopping retatrutide.

Retatrutide is an investigational medicine and is not approved for any use. Its other reported effects are in retatrutide side effects.

Sources

• Coskun T, et al. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. Lancet Diabetes Endocrinol. 2025.
• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1)
• Jastreboff AM, Kaplan LM, Frías JP, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514–526.
• 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.
• Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989–1002.

Medical Disclaimer: This article summarizes published research for general information only and is not medical or nutritional advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and products sold online under its name are not sold or supplied by Lilly. Nothing here is a recommendation to use, seek out or avoid any medication, diet or exercise program.