Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.

In this double-blind, placebo-controlledphase 2, trial, 507 adults with obesity (body mass index ≥30 kg m-2 or ≥27 kg m-2 with at least one obesity-associated complication (excluding diabetes) were randomized to nine groups (1:1:1:1:1:1:1:1:1 ratio) to receive treatment for 48 weeks: placebo, bimagrumab (10 mg kg-1 or 30 mg kg-1 intravenously every 12 weeks), semaglutide (1.0 mg or 2.4 mg subcutaneously once a week) and combinations thereof.

在这项双盲、安慰剂对照的2期试验中，共有507名肥胖成人（体质指数≥30 kg/m²或≥27 kg/m²且至少有一种与肥胖相关的并发症（不包括糖尿病））被随机分为九组（1:1:1:1:1:1:1:1:1比例），接受为期48周的治疗：安慰剂，bimagrumab（10 mg/kg或30 mg/kg静脉注射每12周一次），semaglutide（1.0 mg或2.4 mg皮下注射每周一次）及其组合。

An open-label treatment extension to week 72 followed.

开放标签治疗延长至第72周。

Randomization was stratified by sex across the treatment groups.

治疗组按性别进行分层随机化。

The primary and secondary endpoints were absolute change from baseline in body weight at week 48 and week 72, respectively.

主要终点和次要终点分别是第48周和第72周相对于基线体重的绝对变化。

The least squares mean absolute changes in body weight at week 48 were -9.3 kg (bimagrumab 30 mg kg-1), -14.2 kg (semaglutide 2.4 mg) and -17.8 kg (bimagrumab 30 mg kg-1 plus semaglutide 2.4 mg-that is, high-dose combination) versus -3.3 kg (placebo) (all P < 0.001 versus placebo).

第48周时，体重的最小二乘平均绝对变化分别为：bimagrumab 30 mg kg-1组为-9.3 kg，semaglutide 2.4 mg组为-14.2 kg，以及bimagrumab 30 mg kg-1加semaglutide 2.4 mg（即高剂量组合）组为-17.8 kg，与之相比，安慰剂组为-3.3 kg（所有组与安慰剂相比P < 0.001）。

Continued improvements were observed through week 72.

通过第72周观察到持续的改善。

Common adverse events for bimagrumab included muscle spasms, diarrhea and acne, and semaglutide was associated with nausea, diarrhea, constipation and fatigue.

Bimagrumab常见的不良事件包括肌肉痉挛、腹泻和痤疮，而Semaglutide与恶心、腹泻、便秘和疲劳有关。

Bimagrumab plus semaglutide resulted in substantial reductions in body weight, and safety was consistent with the known safety profiles of both drugs.

Bimagrumab联合semaglutide导致体重显著降低，安全性与这两种药物已知的安全性特征相符。

ClinicalTrials.gov identifier: NCT05616013 .

ClinicalTrials.gov注册号：NCT05616013。