Moiz Areesha, Filion Kristian B, Toutounchi Helia, Tsoukas Michael A, Yu Oriana H Y, Peters Tricia M, Eisenberg Mark J
Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada (A.M.).
Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital; Department of Epidemiology, Biostatistics and Occupational Health, McGill University; and Department of Medicine, McGill University, Montreal, Quebec, Canada (K.B.F.).
Ann Intern Med. 2025 Feb;178(2):199-217. doi: 10.7326/ANNALS-24-01590. Epub 2025 Jan 7.
Recent randomized controlled trials (RCTs) have investigated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual or triple co-agonists for weight loss among adults with overweight or obesity and without diabetes.
To assess the efficacy and safety of GLP-1 RAs and co-agonists for the treatment of obesity among adults without diabetes.
MEDLINE, Embase, and Cochrane CENTRAL from inception to 4 October 2024.
Placebo-controlled RCTs in otherwise healthy participants with overweight or obesity.
The primary outcome was change in relative or absolute body weight from baseline to maximum on-treatment follow-up. Safety outcomes included death, serious adverse events (SAEs), any adverse events (AEs), and gastrointestinal AEs.
A total of 26 RCTs comprising 15 491 participants (72% female; mean body mass index, 30 to 41 kg/m; mean age, 34 to 57 years) and 12 agents (3 commercially available agents [liraglutide, semaglutide, and tirzepatide] and 9 premarket agents for long-term weight management) were included. Treatment ranged from 16 to 104 weeks (median, 43 weeks). Compared with placebo, tirzepatide (15 mg once weekly) resulted in weight loss of up to 17.8% (95% CI, 16.3% to 19.3%) after 72 weeks of therapy; semaglutide (2.4 mg once weekly), up to 13.9% (CI, 11.0% to 16.7%) after 68 weeks; and liraglutide (3.0 mg once daily), up to 5.8% (CI, 3.6% to 8.0%) after 26 weeks. Retatrutide (12 mg once weekly) produced greater weight loss of up to 22.1% (CI, 19.3% to 24.9%) after 48 weeks; other novel single and combination GLP-1 agents were also efficacious to varying degrees. Although AEs were frequent (GLP-1 RA vs. placebo: 80% to 97% vs. 63% to 100%), the majority were gastrointestinal-related (47% to 84% vs. 13% to 63%, respectively), most commonly nausea, vomiting, diarrhea, and constipation. AEs requiring treatment discontinuation (0% to 26% vs. 0% to 9%, respectively) and SAEs (0% to 10% vs. 0% to 12%, respectively) were rare.
No head-to-head RCTs were available. Heterogeneity prevented meta-analysis.
GLP-1 RAs and co-agonists are efficacious for weight loss, with reported safety concerns predominantly gastrointestinal in nature, when used among adults with overweight or obesity and without diabetes.
None. (PROSPERO: CRD42024505558).
近期的随机对照试验（RCT）研究了胰高血糖素样肽-1受体激动剂（GLP-1 RA）以及双重或三重共激动剂在超重或肥胖且无糖尿病的成年人中的减肥效果。
评估GLP-1 RA和共激动剂在无糖尿病成年人中治疗肥胖症的疗效和安全性。
从创刊至2024年10月4日的MEDLINE、Embase和Cochrane CENTRAL。
针对超重或肥胖的健康参与者进行的安慰剂对照RCT。
主要结局是从基线到治疗期间最大随访时相对或绝对体重的变化。安全性结局包括死亡、严重不良事件（SAE）、任何不良事件（AE）以及胃肠道AE。
共纳入26项RCT，涉及15491名参与者（72%为女性；平均体重指数为30至41kg/m；平均年龄为34至57岁）以及12种药物（3种市售药物[利拉鲁肽、司美格鲁肽和替尔泊肽]和9种用于长期体重管理的上市前药物）。治疗时间为16至104周（中位数为43周）。与安慰剂相比，治疗72周后，替尔泊肽（每周一次，15mg）导致体重减轻高达17.8%（95%CI，16.3%至19.3%）；治疗68周后，司美格鲁肽（每周一次，2.4mg）导致体重减轻高达13.9%（CI，11.0%至16.7%）；治疗26周后，利拉鲁肽（每日一次，3.0mg）导致体重减轻高达5.8%（CI，3.6%至8.0%）。治疗48周后，retatrutide（每周一次，12mg）导致体重减轻更多，高达22.1%（CI，19.3%至24.9%）；其他新型单一和联合GLP-1药物也有不同程度的疗效。尽管不良事件很常见（GLP-1 RA与安慰剂相比：80%至97%对63%至100%），但大多数与胃肠道相关（分别为47%至84%对13%至63%），最常见的是恶心、呕吐、腹泻和便秘。需要停药的不良事件（分别为0%至26%对0%至9%）和严重不良事件（分别为0%至10%对0%至12%）很少见。
没有直接比较的RCT。异质性妨碍了荟萃分析。
GLP-1 RA和共激动剂在超重或肥胖且无糖尿病的成年人中使用时对减肥有效，报告的安全问题主要是胃肠道方面的。
无。（国际前瞻性系统评价注册库：CRD42024505558）
