ResearchJun 9, 20260 views

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial.

Tirzepatide gets a lot of attention for driving weight loss, but lean mass loss often comes with it. Researchers just published a phase 2 study testing whether apitegromab — a selective myostatin inhibitor — can help preserve muscle while people are losing weight on tirzepatide. The results: apitegromab actually delivered.

Nat Med

by Pratley RE, Denham DS, Trivedi R et al.

“Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial. Pratley RE(1), Denham DS(2), Trivedi R(3), Watkins E(4), Connery L(5), Barnes J(6), Yu D(6), Hong J(6), Simard C(6), Umans K(6), Liu L(6), Tirucherai GS(6), Marantz JL(6). Author information: (1)AdventHealth Translational Research Institute, Orlando, FL, USA. Richard.Pratley.MD@AdventHealth.com. (2)Flourish Research - San Antonio, San Antonio, TX, USA. (3)Flourish Research - Chicago, Chicago, IL, USA. (4)ProSciento, Inc., Chula Vista, CA, USA. (5)AMR Clinical, Norman, OK, USA. (6)Scholar Rock, Inc., Cambridge, MA, USA. Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg-1) or tirzepatide plus placebo. At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2-2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16 weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63-86%)) and 36 of 51 (71% (57-81%)) participants experiencing an AE, respectively. Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0-10%)) participants in each arm. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier: NCT06445075 . © 2026. The Author(s). Conflict of interest statement: Competing interests: R.E.P. declares speaker fees from Abbott, Corcept, Lilly and Novo Nordisk; consulting fees from AbbVie, Amgen, Bayer AG, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Corcept, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Intas Pharmaceuticals, Lilly, Novo Nordisk, Pfizer, Sun Pharmaceutical Industries and Verdiva; and research grants from Boehringer Ingelheim, Carmot Therapeutics, Dompe, Endogenex, Lilly, Novo Nordisk and Sanofi. D.S.D. reports no conflicts related to this work. R.T. reports no conflicts related to this work. E.W. reports no conflicts related to this work. L.C. has served on advisory boards for Boehringer Ingelheim, Lilly and Intarcia and has received research funding from Amgen, Argo, AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Novo Nordisk, Pfizer, Regeneron, Regor, Roche, Scholar Rock, Structure/Gasherbrum, Vanda, Verdiva, Viking and Zealand. D.Y., J.H., C.S., K.U., L.L., G.S.T. and J.L.M. are employees of Scholar Rock, Inc. and may hold stock/stock options in the company. J.B. was affiliated with Scholar Rock at the time the study was conducted.”

Here’s what happened. 102 adults with overweight or obesity were randomized to receive tirzepatide plus either apitegromab or placebo for 24 weeks. Both groups lost similar amounts of total body weight. But the apitegromab group kept 1.9 kg more lean mass on average compared to the placebo group. That’s about 55% better muscle retention, without blunting the overall weight loss.

Why does this matter? Researchers using tirzepatide for metabolic studies or body composition research have worried about the trade-off between fat loss and muscle preservation. This trial shows you can potentially get both — with the right combination of research compounds.

Key details from the study:

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Apitegromab concentrations increased and stabilized after about 16 weeks, matching the pharmacodynamic marker of total latent myostatin.

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Adverse event rates were similar between the groups. Serious events were balanced and rare.

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The proof-of-concept supports targeting myostatin if you care about muscle during weight loss research.

For anyone researching body recomposition, this is a template for future protocols. Combining myostatin inhibition with incretin mimetics like tirzepatide opens new doors for lean mass retention studies.

Want more on tirzepatide or sourcing research compounds? Check the vendor directory for the latest suppliers. This study gives muscle-minded researchers a reason to watch myostatin inhibitors closely.

Back to News Read original on Nat Med

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial.

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