Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial.

Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking.

临床前和初步人体研究表明，GLP-1受体激动剂司美格鲁肽可能会减少酒精饮用。

This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity.

本研究评估了每周一次使用semaglutide治疗寻求治疗的酒精使用障碍和肥胖共病患者的疗效。

Methods

In a 26-week, single-centre, randomised, double-blinded, placebo-controlledtrial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy.

在这项为期26周的单中心、随机、双盲、安慰剂对照试验中，中度至重度酒精使用障碍和肥胖共病的寻求治疗的参与者被随机分配（1:1），每周一次接受2.4毫克皮下注射的semaglutide或安慰剂（皮下注射生理盐水），同时接受标准的认知行为疗法。

The primary endpoint was a reduction in the number of heavy drinking days assessed after 26 weeks of intervention, analysed with an ANCOVA model.

主要终点是干预26周后重度饮酒天数的减少，使用ANCOVA模型进行分析。

Analysis adhered to the intention-to-treatprinciple, and missing outcome data were addressed using multiple imputations.

分析遵循意向治疗原则，缺失的结果数据通过多重插补法处理。

Safety was assessed in all treated patients.

所有接受治疗的患者均进行了安全性评估。

The trial is registered at ClinicalTrials.govNCT05895643, and is complete.

该试验已在ClinicalTrials.gov上注册，注册号为NCT05895643，并且已经完成。

Results

From June 10, 2023, to Feb 4, 2025, 108 participants (53 women and 55 men) were enrolled, with 54 participants in each of the semaglutide and placebo treatment groups, and all were included in the data analysis.

从2023年6月10日至2025年2月4日，共有108名参与者（53名女性和55名男性）被纳入研究，其中54名参与者分别接受semaglutide和安慰剂治疗，所有参与者均被纳入数据分析。

Overall, 88 participants (81%) completed the full intervention.

总体而言，88名参与者（占81%）完成了整个干预。

Semaglutide was associated with a reduction in heavy drinking days (-41·1 percentage points from baseline, 95% CI -48·7 to -33·5) compared with placebo (-26·4, -34·1 to -18·6; estimated treatment difference -13·7 percentage points, -22·0 to -5·4; p=0·0015), and had substantial effects on multiple secondary alcohol-related and somatic outcomes.

Semaglutide 与减少重度饮酒日相关（从基线起减少41·1个百分点，95% 置信区间为-48·7至-33·5），与安慰剂组相比（减少26·4个百分点，95% 置信区间为-34·1至-18·6；估计治疗差异为-13·7个百分点，95% 置信区间为-22·0至-5·4；p=0·0015），并且对多个次要的与酒精相关和躯体结果有显著影响。

Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group.

不良事件是短暂的，通常是轻度至中度的胃肠道效应，并且在Semaglutide组中更频繁发生。

interpretation

Semaglutide showed robust therapeutic effects in treatment-seeking participants with obesity and alcohol use disorder and this trial supports previous preclinical and clinical findings suggesting GLP-1 receptor agonists as a potential novel treatment target for alcohol use disorder.

Semaglutide在寻求治疗的肥胖和酒精使用障碍参与者中显示出显著的治疗效果，这项试验支持了之前的基础和临床研究结果，表明GLP-1受体激动剂可能是酒精使用障碍的潜在新型治疗靶点。

funding

The Research Foundation, Mental Health Services (Capital Region of Denmark), the Novo Nordisk Foundation, the Novavi Foundation, the Hartmann Foundation, and the Augustinus Foundation.

该研究得到了丹麦首都地区精神卫生服务研究基金会、诺和诺德基金会、诺瓦维基金会、哈特曼基金会和奥古斯都基金会的支持。