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

Pratley RE, Denham DS, Trivedi R, Watkins E, Connery L, Barnes J, Yu D, Hong J, Simard C, Umans K, Liu L, Tirucherai GS, Marantz JL

Nature medicine8 Jun 2026Cited by 9 (Europe PMC)

PMID42260100PMCIDPMC13375528DOI10.1038/s41591-026-04440-4PepBankPUB-42260100

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Summary

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 .

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone5

In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Tirzepatide.

01HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with overweight or obesity taking tirzepatide, adding apitegromab gave 1.9 kg less lean mass loss than adding placebo at week 24.
In plain wordsIn adults with overweight or obesity taking tirzepatide, apitegromab reduced loss of lean mass compared with placebo at 24 weeks.
Peptide
Tirzepatide
Outcome
DecreaseLean mass loss at week 24
Study
n = 102
Comparator
Tirzepatide plus placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Difference in lean mass loss
1.9 kg
apitegromab vs placebo, week 24
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4226010001
02HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with overweight or obesity taking tirzepatide, total body weight loss was similar with apitegromab and with placebo at week 24.
In plain wordsIn adults taking tirzepatide, total weight loss was similar with apitegromab and with placebo.
Peptide
Tirzepatide
Outcome
No significant changeTotal body weight loss at week 24
Study
n = 102
Comparator
Tirzepatide plus placebo
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4226010002
03HumanNot a test of Tirzepatide aloneRandomized controlled trialPharmacokinetics
In adults taking tirzepatide plus apitegromab, trough concentrations of apitegromab and total latent myostatin both increased over time and reached a plateau after approximately 16 weeks.
In plain wordsIn adults taking tirzepatide plus apitegromab, apitegromab levels and a muscle marker rose over time and levelled off after about 16 weeks.
Peptide
Tirzepatide
Outcome
IncreaseApitegromab and latent myostatin concentrations
Study
n = 102
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4226010003
04HumanNot a test of Tirzepatide aloneRandomized controlled trialSafety outcome
In adults taking tirzepatide, the incidence of adverse events was generally similar with apitegromab (39 of 51) and with placebo (36 of 51).
In plain wordsIn adults taking tirzepatide, side effects occurred about equally often with apitegromab and with placebo.
Peptide
Tirzepatide
Outcome
No significant changeAdverse events incidence
Study
n = 102
Comparator
Tirzepatide plus placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4226010004
05HumanNot a test of Tirzepatide aloneRandomized controlled trialSafety outcome
In adults taking tirzepatide, serious adverse events were balanced, with one of 51 participants in each arm.
In plain wordsIn adults taking tirzepatide, serious side effects were rare and equal in both arms: one person each.
Peptide
Tirzepatide
Outcome
No significant changeSerious adverse events
Study
n = 102
Comparator
Tirzepatide plus placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0-10%)) participants in each arm.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4226010005

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT06445075

Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese

Scholar Rock, Inc.n = 10221 May 2024 to 17 Jun 2025

Overweight and Obesity

Trial page ClinicalTrials.govUpdated 23 Jan 2026

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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