Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial
- Design
- Randomized trial · 102 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationObesity; the trial exists because lean-mass loss with tirzepatide is substantial (about 3.5 kg in 24 weeks in the placebo arm, inferred).
- Could weight loss explain it?
- Not applicable[Auto] Harm signal; weight-loss mediation not the relevant question, but consider whether harms relate to rapid weight loss or reduced intake.
- Study tier
- Study tier 3Small proof-of-concept phase 2.
- Assessment
- Version 2 · curated · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
A 24-week trial added a myostatin-blocking antibody to tirzepatide and preserved about half of the lean mass that would otherwise be lost. Its main relevance here is as confirmation that meaningful lean-mass loss accompanies incretin-induced weight loss; muscle function was not measured.
01Findings
What the study reported
- Drugs
- Tirzepatide
- Dose
- tirzepatide plus apitegromab 10 mg/kg or placebo
- Treatment duration
- 24 weeks
- Comparator
- tirzepatide plus placebo
- Primary outcome
- Lean mass change at week 24
- Effect
- 1.9 kg less lean-mass loss with apitegromab (54.9% retention relative to placebo) at similar total weight loss
- 95% confidence interval
- 1.2 to 2.7 (80% CI)
- P value
- 0.001
- Follow-up
- 24 weeks
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Obesity status
- overweight or obesity required
- Sample size
- 102
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 102
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 16 weeks
- Outcome type
- DXA lean mass; no function outcome
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- n=102; 80% CI reported
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Scholar Rock (apitegromab developer; full text)
- Industry funded
- Yes
- Manufacturer
- Scholar Rock (not a GLP-1 manufacturer); tirzepatide by Eli Lilly
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Lead author reports fees from Lilly, Novo Nordisk and others.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- GLP-1-induced weight loss causes clinically meaningful loss of muscle mass or function.Supports
EMBRAZE: apitegromab preserved ~55% of lean mass otherwise lost with tirzepatide; confirms lean-mass loss occurs.
04Source
The source, as retrieved
Abstract
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 .
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 42260100 first ingestion |