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Can a Drug Prevent Muscle Loss on a GLP-1? Two Antibodies Tested

Not outside a trial. Apitegromab kept 1.9 kg more lean mass on tirzepatide without slowing weight loss, and bimagrumab added lean mass on its own. Neither is approved, and nobody measured strength.

Dana Sullivan7 min read
Week 24, both arms on tirzepatide1.9 kg less lean mass lost80% CI 1.2 to 2.7 — an 80% interval, not 95%Total weight lost: similar in both arms.Strength or physical function: not measured.102 participants · phase 2 · investigational, not on sale

Not yet, outside a trial. The closest result so far comes from apitegromab, an antibody given with tirzepatide to 102 adults. At 24 weeks it left 1.9 kg less lean mass lost than placebo, and total weight loss was similar in both arms [1]. A second antibody, bimagrumab, has two phase 2 trials behind it [2] [3]. Neither drug is approved, and neither can be bought.

The problem both are aimed at is real. Lean mass is lost in proportion to total weight on drugs such as tirzepatide [1]. The muscle loss guide sets out how much goes and what comes back after stopping. The approaches with evidence today are protein and resistance training. A drug would be a third option, and a second prescription.

Apitegromab: lean mass kept, weight loss unchanged

Apitegromab blocks the activation of myostatin, the signal that limits how much muscle the body builds. In the EMBRAZE trial, adults with overweight or obesity all took tirzepatide and were randomized 1:1 to add apitegromab or placebo [1]. At week 24 the apitegromab group had lost 1.9 kg less lean mass than placebo (P = 0.001). The authors describe that as retaining 54.9% of the lean mass that would otherwise have gone.

The part that mattered most was the weight. Total weight loss was similar between the arms, so the lean mass was retained without blunting what tirzepatide took off. Adverse events ran 39 of 51 on apitegromab against 36 of 51 on placebo. The authors call it a proof-of-concept study, and 51 people per arm over 24 weeks can only detect common problems.

Bimagrumab: fat down, lean mass up, and then a combination

Bimagrumab blocks a different target, the activin type II receptor, and blocking that signal stimulates skeletal muscle growth. The first trial gave it alone, with no GLP-1, to 75 adults with type 2 diabetes and a BMI of 28 to 40 [3]. After 48 weeks of monthly infusions, fat mass fell 20.5% (−7.5 kg) against 0.5% on placebo. Lean mass rose 3.6% (1.70 kg, 80% CI 1.1 to 2.3) against a 0.8% fall on placebo, and body weight fell 6.5%.

That is a gain in lean mass while weight fell. Two limits sit beside it. Only 58 of the 75 completed the 48 weeks, and only participants who completed the full regimen were analyzed. Every interval is again 80%.

The larger BELIEVE trial then paired bimagrumab with semaglutide [2]. It randomized 507 adults with obesity across nine groups for 48 weeks. Body weight fell 9.3 kg on the higher bimagrumab dose alone, 14.2 kg on semaglutide 2.4 mg alone, and 17.8 kg on the high-dose combination, against 3.3 kg on placebo. Its primary endpoint was weight, not lean mass, so it answers whether the two drugs add up on the scale. They did. Muscle spasms, diarrhea and acne were the common side effects of bimagrumab.

What none of these trials measured

Lean mass on a DXA scan includes organs and body water alongside skeletal muscle. None of the three trials reports grip strength, walking speed or any measure of physical function. What was preserved is a compartment on a scan, not a demonstrated ability to lift or carry anything. The same gap runs through the field, as the grip strength evidence shows: mass and strength do not always move together.

The people most likely to need a muscle-sparing drug are older adults, and the trade-offs for them are set out in the analysis in older adults. For now the practical answer has not changed, and it starts with food: how much less people eat shows the size of that fall. The broader case on muscle is in what these drugs do to muscle.

Frequently asked

Is there a drug to prevent muscle loss on a GLP-1?
Not one that is approved or on sale. Apitegromab and bimagrumab are investigational antibodies that have been tested in phase 2 trials. Protein intake and resistance training remain the approaches with evidence behind them.
How much muscle did apitegromab save?
In 102 adults on tirzepatide, the apitegromab group lost 1.9 kg less lean mass than placebo at 24 weeks, with an 80% confidence interval of 1.2 to 2.7 kg. Total weight loss was similar in both groups.
Does bimagrumab work with semaglutide?
On weight, yes. In a 507-person trial the combination took off 17.8 kg at 48 weeks against 14.2 kg on semaglutide 2.4 mg alone and 3.3 kg on placebo. That trial's primary endpoint was body weight rather than lean mass.
Did either drug preserve strength?
Unknown. The trials measured lean mass on a scan, which includes organs and body water, and reported no grip strength, walking speed or physical function outcome.

Sources

  1. [1] Pratley RE, Denham DS, Trivedi R, Watkins E, et al. (2026). Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial Nature Medicine. PMID 42260100
  2. [2] Heymsfield SB, Aronne LJ, Montgomery P, Klickstein LB, et al. (2026). Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial Nature Medicine. PMID 41772149
  3. [3] Heymsfield SB, Coleman LA, Miller R, Rooks DS, et al. (2021). Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial JAMA Network Open. PMID 33439265

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