Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial
6 affiliations
- 1AdventHealth Translational Research Institute, Orlando, FL, USA. [email protected]
- 2Flourish Research - San Antonio, San Antonio, TX, USA
- 3Flourish Research - Chicago, Chicago, IL, USA
- 4ProSciento, Inc., Chula Vista, CA, USA
- 5AMR Clinical, Norman, OK, USA
- 6Scholar Rock, Inc., Cambridge, MA, USA
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 .
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BibTeX
@article{pratley2026apitegromab,
title = {{Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial}},
author = {Richard E. Pratley and Douglas Scott Denham and Rupal Trivedi and Elaine Watkins and Lisa Connery and Jennifer Barnes and Dongzi Yu and Janet Hong and Christopher Simard and Kimberly Umans and Lan Liu and Giridhar Tirucherai and Jing L. Marantz},
journal = {Nature Medicine},
year = {2026},
month = jun,
doi = {10.1038/s41591-026-04440-4},
url = {https://doi.org/10.1038/s41591-026-04440-4},
note = {CC BY},
}
RIS
TY - JOUR
TI - Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial
AU - Richard E. Pratley
AU - Douglas Scott Denham
AU - Rupal Trivedi
AU - Elaine Watkins
AU - Lisa Connery
AU - Jennifer Barnes
AU - Dongzi Yu
AU - Janet Hong
AU - Christopher Simard
AU - Kimberly Umans
AU - Lan Liu
AU - Giridhar Tirucherai
AU - Jing L. Marantz
PY - 2026
DA - 2026/06/08
JO - Nature Medicine
DO - 10.1038/s41591-026-04440-4
UR - https://doi.org/10.1038/s41591-026-04440-4
AB - 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 .
SN - 1078-8956
SN - 1546-170X
SN - 1744-7933
ER -