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

Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass.

Apitegromab是一种正在研究中的完全人源化单克隆抗体，它选择性地抑制肌抑素激活，因此能够增加肌肉质量。

In the randomized, double-blind, placebo-controlledphase 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.

在随机、双盲、安慰剂对照的EMBRAZE研究第二阶段中，将102名超重或肥胖的成人按1:1的比例随机分配接受tirzepatide加apitegromab（10 mg kg-1）或tirzepatide加安慰剂治疗。

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.

在第24周时，apitegromab导致的瘦体重损失的最小二乘平均值（80%置信区间（CI））为1.9（1.2-2.7）kg，比安慰剂少（P = 0.001），尽管两组的总体重损失相似，这代表了与安慰剂相比瘦体重的54.9%的保留。

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.

在接受apitegromab治疗的参与者中，apitegromab的谷浓度和总潜在肌肉生长抑制素（一种药效学标志物）随时间增加，并在大约16周后达到平稳。

Incidenceof 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.

不良事件（AEs）的发生率（% (95% CI)）在apitegromab治疗参与者和安慰剂治疗参与者之间大致相似，分别有51名参与者中的39名（76% (63-86%)）和51名参与者中的36名（71% (57-81%)）经历了不良事件。

Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0-10%)) participants in each arm.

严重不良事件（SAEs）在每组中平衡发生，每组各有1名参与者（2%（0-10%））经历了SAEs。

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.

总之，这项概念验证研究证明了通过apitegromab选择性靶向肌肉生长抑制素与tirzepatide联合使用时，能够良好耐受并有效保持瘦体重。

ClinicalTrials.gov identifier: NCT06445075 .

临床试验注册号：NCT06445075。