Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.

Methods

Systematic reviewand network meta-analysisof 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.

采用频率随机效应模型和贝叶斯剂量反应模型进行系统评价和网络荟萃分析，涉及24个结果指标，使用GRADE（推荐等级的评估、制定与评价）方法和Cochrane偏倚风险工具2。

data_sources

Medline, Embase, and Cochrane Library, searched up to 12 November 2025.

检索了Medline、Embase和Cochrane图书馆，截至2025年11月12日。

study_selection

Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.

比较一种或多种药物与生活方式改变、安慰剂或另一种药物的随机对照试验，持续时间至少12周或更长。

Results

This network meta-analysiscomprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.

这项网络荟萃分析包括了262项试验（99,791名参与者），评估了19种药物，随访时间从12周到172周。

Compared with lifestyle modification alone, at one year, moderate to high certainty evidence shows substantial weight loss with tirzepatide (mean difference -14.9%, 95% confidence interval-16.0% to -13.9%), cagrilintide-semaglutide (CagriSema, -14.8%, -16.9% to -12.7%), oral semaglutide (-10.9%, -12.7% to -9.1%), orforglipron (-9.9%, -12.4% to -7.5%), subcutaneous semaglutide (-9.8%, -10.6% to -9.1%), and phentermine-topiramate (-8.1%, -9.7% to -6.5%).

与仅生活方式改变相比，一年后，中等到高度证据表明，使用tirzepatide（平均差异-14.9%，95%置信区间-16.0%至-13.9%）、cagrilintide-semaglutide（CagriSema，-14.8%，-16.9%至-12.7%）、口服semaglutide（-10.9%，-12.7%至-9.1%）、orforglipron（-9.9%，-12.4%至-7.5%）、皮下注射semaglutide（-9.8%，-10.6%至-9.1%）和phentermine-topiramate（-8.1%，-9.7%至-6.5%）可显著减轻体重。

Emerging agents (ecnoglutide, mazdutide, retatrutide) may produce similar or greater reductions (13.1-14.6%; very low to low certainty).

新兴药物（ecnoglutide, mazdutide, retatrutide）可能会产生相似或更大的降低效果（13.1-14.6%；非常低到低确定性）。

Moderate to high certainty evidence supports discontinuation because of adverse events to be highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide (risk ratios from 1.9 to 4.2); gastrointestinal events were most increased with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (risk ratios from 3.1 to 4.2).

中等到高度确定性的证据支持，因不良事件而停药的可能性最高的是orfglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema和口服semaglutide（风险比从1.9到4.2）；胃肠道事件增加最多的是naltrexone-bupropion, 口服semaglutide, orfglipron和tirzepatide（风险比从3.1到4.2）。

Fatigue risk increased, particularly with naltrexone-bupropion (risk ratio 8.9; absolute increase 331 per 1000 people over one year), orforglipron (3.4; 100 more per 1000), and CagriSema (3.2; 92 more per 1000).

疲劳风险增加，特别是使用纳曲酮-安非他酮（风险比为8.9；一年内每1000人中绝对增加331人），或forglipron（3.4；每1000人中增加100人），以及CagriSema（3.2；每1000人中增加92人）。

Tirzepatide reduced fat mass the most (by 25.7%) but also lean mass the most (by 8.3%).

Tirzepatide最大程度减少了脂肪质量（减少了25.7%），但同时也最大程度减少了瘦体质量（减少了8.3%）。

Subcutaneous semaglutide was the only drug associated with reduced all cause mortality (risk ratio 0.81, 95% confidence interval0.72 to 0.93) and myocardial infarction (0.72, 0.61 to 0.85), with these estimates largely informed by cardiovascular outcome trials in high risk populations.

皮下注射司美格鲁肽是唯一与降低全因死亡率（风险比0.81，95%置信区间0.72至0.93）和心肌梗死（0.72，0.61至0.85）相关的药物，这些估计主要由高风险人群的心血管结果试验提供信息。

Subcutaneous semaglutide (0.43, 0.21 to 0.84) and tirzepatide (0.49, 0.27 to 0.88) reduced heart failure risk.

皮下注射司美格鲁肽（0.43，0.21至0.84）和tirzepatide（0.49，0.27至0.88）降低了心力衰竭的风险。

No drugs convincingly reduced kidney failure or improved quality of life (43 trials with 45 663 participants) beyond established minimally important differences (all mean differences <5 points; minimally important difference 10).

没有药物显著降低肾衰竭或改善生活质量（43项试验，共45,663名参与者），超出已确立的最小重要差异（所有平均差异<5分；最小重要差异为10分）。

Except for larger weight reductions in trials with longer duration (shown for subcutaneous semaglutide), subgroup analyses for drug dosages and key patient characteristics did not identify credible differences in relative effects of treatment.

除了在持续时间更长的试验中观察到更大的体重减轻（皮下注射司美格鲁肽显示），对于药物剂量和关键患者特征的亚组分析并未发现治疗相对效果的可信差异。

Conclusions

Obesity drugs produce variable weight loss at one year, with larger benefits generally accompanied by greater harms and discontinuation.

肥胖药物在一年内的减重效果各异，通常更大的益处伴随着更大的危害和停药率。

Most agents do not improve quality of life meaningfully and few show cardiovascular benefits.

大多数药物未能显著改善生活质量，且很少有药物显示出心血管益处。

Decisions in clinical practice should consider trade-offs between benefits and harms within the context of shared decision making.

在临床实践中，应在共享决策的背景下考虑利益与危害之间的权衡。

systematic_review_registration

PROSPERO CRD42024507993.

PROSPERO CRD42024507993。