Effects of semaglutide on cardiovascular outcomes in patients with obesity with or without diabetes: a meta-analysis based on randomized controlled trials
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摘要: 目的 探讨司美格鲁肽对伴或不伴糖尿病的肥胖症患者心血管预后的影响。方法 检索Pubmed、Embase和Cochrane图书馆的数据库，纳入体重指数(BMI)>30 kg/m2、伴或不伴糖尿病的患者，使用RevMan 5.4进行荟萃分析。结果 最终纳入7项随机对照研究，共计29 275例。与安慰剂相比，在伴或不伴糖尿病的肥胖症患者中，司美格鲁肽显著减少主要不良心血管事件(major adverse cardiovascular events，MACE)(OR=0.81，95%CI：0.74~0.88，P < 0.001)、全因死亡(OR=0.80，95%CI：0.72~0.89，P < 0.001)、心血管死亡(OR=0.80，95%CI：0.69~0.92，P=0.001)、心力衰竭(OR=0.86，95%CI：0.75~0.99，P=0.04)和严重不良事件(OR=0.86，95%CI：0.82~0.90，P < 0.001)。与安慰剂相比，司美格鲁肽导致治疗中断的不良事件发生率明显升高(OR=1.63，95%CI：1.20~2.20，P=0.002)。结论 司美格鲁肽可降低MACE、全因死亡、心血管死亡、心力衰竭以及严重不良事件的发生率，但会增加治疗中断的不良事件。Abstract: Objective To explore the effect of semaglutide on cardiovascular outcomes in obese patients with or without diabetes.Methods Databases from Pubmed, Embase and the Cochrane Library were searched. We recruited patients with a body mass index(BMI) greater than 30 kg/m2, with or without diabetes. A meta-analysis was performed using RevMan 5.4.Results A total of 7 randomized controlled trials involving 29 275 participants were included. Compared to placebo, semaglutide significantly reduced major adverse cardiovascular events(MACE) in obese patients with or without diabetes(OR=0.81, 95%CI: 0.74 to 0.88, P < 0.001). It also reduced all-cause mortality(OR=0.80, 95%CI: 0.72 to 0.89, P < 0.001), cardiovascular mortality(OR=0.80, 95%CI: 0.69 to 0.92, P=0.002), heart failure(OR=0.86, 95%CI: 0.75 to 0.99, P=0.04), and serious adverse events(OR=0.86, 95%CI: 0.82 to 0.90, P < 0.001). However, semaglutide was associated with a significantly higher incidence of adverse events leading to treatment discontinuation compared to placebo(OR=1.63, 95%CI: 1.20 to 2.20, P=0.002).Conclusion Semaglutide may reduce the incidence of MACE, all-cause mortality, cardiovascular mortality, heart failure, and serious adverse events, but it increases the risk of adverse events leading to treatment discontinuation.
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Key words:
- semaglutide /
- cardiovascular outcomes /
- obesity /
- diabetes
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图 3 心血管死亡发生的森林图
Figure 3. The forest plot for the occurrence of cardiovascular mortality
图 6 严重不良事件发生的森林图
Figure 6. The forest plot for the occurrence of serious adverse events
图 7 导致治疗中断的不良事件的森林图
Figure 7. The forest plot for adverse events leading to treatment discontinuation
图 9 严重不良事件相关研究的漏斗图
Figure 9. The funnel plot for serious adverse events related studies
表 1 纳入研究的基本特征
Table 1. Basic information of included studies
例(%), X±S 项目 SUSTAIN-6 (2016)[17] PIONEER 6 (2019)[18] SELECT (2023)[19] OASIS 1 (2023)[20] STEP-HFpEF DM (2024)[21] FLOW (2024)[22] STEP 7 (2024)[23] 用药方式 每周1次(0.5或1.0 mg)或安慰剂，疗程104周 每天1次口服(目标剂量14 mg)或安慰剂 每周1次，每次0.24 mg，每4周增加1次，直至16周后达到2.4 mg的目标剂量 口服，剂量增至50 mg，或相同剂量的安慰剂，每天1次，连续68周，同时进行生活方式干预 前4周，每周1次，每次0.25 mg，后每4周增加1次，直至16周后达到2.4 mg的目标剂量 采用为期8周的剂量递增方案，剂量递增(只要不出现不可接受的不良反应)从每周0.25 mg开始，持续4周，再持续4周，每周0.5 mg，然后在剩余的治疗期内维持每周1.0 mg 每周1次皮下注射2.4 mg或安慰剂，持续44周，同时接受饮食和体育锻炼干预 例数 3 297 3 183 17 604 667 616 3 533 375 男性 2 002(60.7) 2 177(68.4) 12 728(72.3) 182(27) 343(55.7) 2 464(69.7) 205(55) 年龄/岁 64.6±7.4 66±7 61.6±8.9 50±13 69±6 66.6±9.0 41±11 体重/kg 92.1±20.6 90.9±21.2 96.6±17.7 105.4±22.2 89.6±20.5 96.4±17.7 BMI/(kg/m2) 32.3±6.5 33.3±5.0 37.5±6.5 36.9±4.6 32.0±6.3 34±4.8 2型糖尿病 100 100 0 0 100 100 糖化血红蛋白/% 8.7±1.4 8.2±1.6 5.8±0.3 5.6±0.3 6.8±0.9 7.8±1.3 6.3±1.1 收缩压/mmHg 135.6±17.1 135±18 131.0±15.4 129±15 138.6±15.8 127±14 舒张压/mmHg 77.1±9.8 76±10 79.3±9.9 82±11 76.4±10.0 84±10 低密度脂蛋白/(mg/dL) 82.4±45.5 78.0±43.1 78.0±42.8 111.5±32.7 100±33 既往心肌梗死 1 072(32.5) 11 900(67.6) 既往卒中 491(14.9) 3 134(17.8) 808(22.9) 既往心力衰竭 777(23.6) 616(100) 678(19.2) 随访时间/年 2 1.6 4 1.3 1 3.4 0.8 
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