Importance Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management. Objective To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity. Design, Setting, and Participants Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338). Interventions Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity. Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration. Placebo groups were pooled (n = 85). Main Outcomes and Measures The primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68. Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups. Comparisons of active treatments vs pooled placebo were supportive secondary end points. Results Of 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment. The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001); weight change with pooled placebo was -1.9%. Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001). Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide. Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide. Conclusions and Relevance Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks. Trial Registration ClinicalTrials.gov Identifier: NCT04074161.

中文翻译：

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每周皮下注射 Semaglutide 与每日利拉鲁肽对无糖尿病超重或肥胖成人体重的影响：STEP 8 随机临床试验。

Importance 3 期试验尚未比较可用于体重管理的胰高血糖素样肽 1 类似物 semaglutide 和利拉鲁肽。目的 比较每周一次皮下注射 semaglutide 2.4 mg 与每天一次皮下注射 liraglutide 3.0 mg（包括饮食和体力活动）在超重或肥胖人群中的疗效和不良事件概况。设计、设置和参与者 2019 年 9 月（入组时间：9 月 11 日至 11 月 26 日）至 2021 年 5 月（随访结束时间：5 月 11 日）在美国 19 个地点进行的随机、开放标签、为期 68 周的 3b 期试验体重指数为 30 或更高或 27 或更高且有 1 种或多种与体重相关的合并症且没有糖尿病的成年人 (N = 338)。干预措施参与者被随机分配 (3:1:3:1) 接受每周一次皮下注射 semaglutide，2.4 mg（16 周递增；n = 126），或匹配的安慰剂，或每天一次皮下注射利拉鲁肽 3.0 mg（4 周递增；n = 127），或匹配的安慰剂，加上饮食和身体活动。无法耐受 2.4 mg 索马鲁肽的参与者可以接受 1.7 mg；无法耐受 3.0 mg 利拉鲁肽的参与者停止了治疗，并可以重新开始 4 周的剂量调整。合并安慰剂组 (n = 85)。主要结局和测量 主要终点是体重的百分比变化，确认性次要终点是体重减轻 10% 或更多、15% 或更多以及 20% 或更多，在第 68 周时对索马鲁肽与利拉鲁肽进行评估。 Semaglutide 与利拉鲁肽的比较是开放标签的，活性治疗组与匹配的安慰剂组双盲。积极治疗与合并安慰剂的比较是支持性的次要终点。结果 338 名随机参与者（平均 [SD] 年龄，49 [13] 岁；265 名女性 [78.4%]；平均 [SD] 体重，104.5 [23.8] 公斤；平均 [SD] 体重指数，37.5 [6.8] )，319 人 (94.4%) 完成了试验，271 人 (80.2%) 完成了治疗。与基线相比，semaglutide 组的平均体重变化为 -15.8%，利拉鲁肽组为 -6.4%（差异，-9.4 个百分点 [95% CI，-12.0 至 -6.8]；P < .001）；混合安慰剂的体重变化为-1.9%。与利拉鲁肽相比，semaglutide 与利拉鲁肽相比，参与者实现 10% 或更多、15% 或更多和 20% 或更多体重减轻的几率显着更高（70.9% 的参与者 vs 25.6% [优势比，6.3 {95% CI，3.5 至 11.2} ]、55.6% 对 12.0% [比值比，7.9 {95% CI，4.1 至 15.4}]，以及 38.5% 对 6.0% [比值比，8.2 {95% CI，3.5 至 19.1}]；所有 P < .001）。因任何原因停止治疗的参与者比例分别为 13.5% 和利拉鲁肽 27.6%。索马鲁肽组和利拉鲁肽组分别报告了 84.1% 和 82.7% 的胃肠道不良事件。结论和相关性 在没有糖尿病的超重或肥胖成人中，与每日一次皮下利拉鲁肽相比，每周一次皮下注射 semaglutide，加上饮食和身体活动咨询，可在 68 周时显着减轻体重。试验注册 ClinicalTrials.gov 标识符：NCT04074161。每周一次皮下注射索马鲁肽与每天一次皮下注射利拉鲁肽相比，加上饮食和体力活动咨询，在 68 周时体重减轻明显更多。试验注册 ClinicalTrials.gov 标识符：NCT04074161。每周一次皮下注射索马鲁肽与每天一次皮下注射利拉鲁肽相比，加上饮食和体力活动咨询，在 68 周时体重减轻明显更多。试验注册 ClinicalTrials.gov 标识符：NCT04074161。