Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial

医学 安慰剂 兴奋剂 胰高血糖素样肽1受体 利拉鲁肽 胰高血糖素样肽-1 双盲 内科学 糖尿病 药理学 内分泌学 2型糖尿病 受体 替代医学 病理
作者
Carel W. le Roux,Oren Steen,Kathryn Jean Lucas,Elena Startseva,Anna Unseld,Anita M. Hennige
出处
期刊:The Lancet Diabetes & Endocrinology [Elsevier BV]
卷期号:12 (3): 162-173 被引量:82
标识
DOI:10.1016/s2213-8587(23)00356-x
摘要

Summary

Background

Obesity is a widespread and chronic condition that requires long-term management; research into additional targets to improve treatment outcomes remains a priority. This study aimed to investigate the safety, tolerability, and efficacy of glucagon receptor–GLP-1 receptor dual agonist survodutide (BI 456906) in obesity management.

Methods

In this randomised, double-blind, placebo-controlled, dose-finding phase 2 trial conducted in 43 centres in 12 countries, we enrolled participants (aged 18–75 years, BMI ≥27 kg/m2, without diabetes) and randomly assigned them by interactive response technology (1:1:1:1:1; stratified by sex) to subcutaneous survodutide (0·6, 2·4, 3·6, or 4·8 mg) or placebo once-weekly for 46 weeks (20 weeks dose escalation; 26 weeks dose maintenance). The primary endpoint was the percentage change in bodyweight from baseline to week 46. Primary analysis included the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of trial medication and who had analysable data for at least one efficacy endpoint) and was based on the dose assigned at randomisation (planned treatment), including all data censored for COVID-19-related discontinuations; the sensitivity analysis was based on the actual dose received during maintenance phase (actual treatment) and included on-treatment data. Safety analysis included all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov (NCT04667377) and EudraCT (2020–002479–37).

Findings

Between March 30, 2021, and Nov 11, 2021, we enrolled 387 participants; 386 (100%) participants were treated (0·6 mg, n=77; 2·4 mg, n=78; 3·6 mg, n=77; 4·8 mg, n=77; placebo n=77) and 233 (60·4%) of 386 completed the 46-week treatment period (187 [61%] of 309 receiving survodutide; 46 [60%] of 77 receiving placebo). When analysed according to planned treatment, mean (95% CI) changes in bodyweight from baseline to week 46 were −6·2% (−8·3 to −4·1; 0·6 mg); −12·5% (−14·5 to −10·5; 2·4 mg); −13·2% (−15·3 to −11·2; 3·6 mg); −14·9% (−16·9 to −13·0; 4·8 mg); −2·8% (−4·9 to −0·7; placebo). Adverse events occurred in 281 (91%) of 309 survodutide recipients and 58 (75%) of 77 placebo recipients; these were primarily gastrointestinal in 232 (75%) of 309 survodutide recipients and 32 (42%) of 77 placebo recipients.

Interpretation

All tested survodutide doses were tolerated, and dose-dependently reduced bodyweight.

Funding

Boehringer Ingelheim.
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