Abstract：
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).
RESULTS: 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.
CONCLUSIONS: All tested survodutide doses were tolerated, and dose-dependently reduced bodyweight.
BACKGROUND: Boehringer Ingelheim.
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).
RESULTS: 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.
CONCLUSIONS: All tested survodutide doses were tolerated, and dose-dependently reduced bodyweight.
BACKGROUND: Boehringer Ingelheim.
摘要：
背景：肥胖是一种广泛的慢性疾病，需要长期管理；研究其他目标以改善治疗结果仍然是当务之急。本研究旨在探讨其安全性，耐受性,胰高血糖素受体-GLP-1受体双重激动剂survodutide（BI456906）在肥胖管理中的疗效。
方法：在这个随机的，双盲,安慰剂对照,在12个国家的43个中心进行的剂量发现2期试验，我们招募了参与者（年龄在18-75岁，BMI≥27kg/m2，无糖尿病），并通过交互式反应技术（1：1：1：1：1：1；按性别分层）将其随机分配至皮下舒托肽（0·6、2·4、3·6或4·8mg）或安慰剂，每周一次，共46周（20周剂量递增；26周剂量维持）。主要终点是从基线到第46周的体重变化百分比。主要分析包括修改后的意向治疗人群（定义为所有随机分配的患者，这些患者接受了至少一个剂量的试验药物，并且具有至少一个疗效终点的可分析数据），并且基于随机分配的剂量（计划治疗）。包括对COVID-19相关停药的所有截尾数据;敏感性分析基于维持期(实际治疗)期间接受的实际剂量,并包括治疗中数据.安全性分析包括接受至少一剂研究药物的所有参与者。该试验已在ClinicalTrials.gov（NCT04667377）和EudraCT（2020-002479-37）注册。
结果：在2021年3月30日至2021年11月11日之间，我们招募了387名参与者；386名（100％）参与者接受了治疗（0.6mg，n=77；2·4毫克，n=78；3·6毫克，n=77；4·8毫克，n=77；安慰剂n=77）和386人中的233（60·4％）完成了46周的治疗期（接受舒洛度肽的309人中有187[61％]；接受安慰剂的77人中有46[60％]）。当根据计划的治疗进行分析时，从基线到第46周的平均体重变化（95％CI）为-6·2％（-8·3至-4·1；0·6mg）；-12·5％（-14·5至-10·5；2·4mg）；-13·2％（-15·3至-11·2；3·6mg）；-14·9％（-16·9-13·0；4-8不良事件发生在309名survodutide接受者的281名（91％）和77名安慰剂接受者的58名（75％）中；这些主要是胃肠道的309名survodutide接受者的232名（75％）和77名安慰剂接受者的32名（42％）。
结论：所有测试的survodutide剂量均耐受，和剂量依赖性地降低体重。
背景：勃林格红.
方法：在这个随机的，双盲,安慰剂对照,在12个国家的43个中心进行的剂量发现2期试验，我们招募了参与者（年龄在18-75岁，BMI≥27kg/m2，无糖尿病），并通过交互式反应技术（1：1：1：1：1：1；按性别分层）将其随机分配至皮下舒托肽（0·6、2·4、3·6或4·8mg）或安慰剂，每周一次，共46周（20周剂量递增；26周剂量维持）。主要终点是从基线到第46周的体重变化百分比。主要分析包括修改后的意向治疗人群（定义为所有随机分配的患者，这些患者接受了至少一个剂量的试验药物，并且具有至少一个疗效终点的可分析数据），并且基于随机分配的剂量（计划治疗）。包括对COVID-19相关停药的所有截尾数据;敏感性分析基于维持期(实际治疗)期间接受的实际剂量,并包括治疗中数据.安全性分析包括接受至少一剂研究药物的所有参与者。该试验已在ClinicalTrials.gov（NCT04667377）和EudraCT（2020-002479-37）注册。
结果：在2021年3月30日至2021年11月11日之间，我们招募了387名参与者；386名（100％）参与者接受了治疗（0.6mg，n=77；2·4毫克，n=78；3·6毫克，n=77；4·8毫克，n=77；安慰剂n=77）和386人中的233（60·4％）完成了46周的治疗期（接受舒洛度肽的309人中有187[61％]；接受安慰剂的77人中有46[60％]）。当根据计划的治疗进行分析时，从基线到第46周的平均体重变化（95％CI）为-6·2％（-8·3至-4·1；0·6mg）；-12·5％（-14·5至-10·5；2·4mg）；-13·2％（-15·3至-11·2；3·6mg）；-14·9％（-16·9-13·0；4-8不良事件发生在309名survodutide接受者的281名（91％）和77名安慰剂接受者的58名（75％）中；这些主要是胃肠道的309名survodutide接受者的232名（75％）和77名安慰剂接受者的32名（42％）。
结论：所有测试的survodutide剂量均耐受，和剂量依赖性地降低体重。
背景：勃林格红.
