Abstract：
Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes. MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks. The primary outcome was a change in relative body weight from baseline to the longest follow-up. Random-effects models with inverse variance weighting were used to estimate the weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). A total of 4 randomized controlled trials (n = 3,087) were included. Of the 3 trials that provided body mass index by category (n = 2,783), 94.0% of the participants had a baseline body mass index ≥30 kg/m2. Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68); however, the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes.
摘要：
塞马鲁肽,胰高血糖素样肽-1受体激动剂，在2型糖尿病患者中已经证明了临床上重要的减肥效果。然而,其对非糖尿病患者持续体重减轻的影响尚不清楚.我们的目的是研究在超重/肥胖和无糖尿病的个体中使用司马鲁肽减肥的长期疗效和安全性。MEDLINE,Embase,系统搜索Cochrane图书馆,以确定随机对照试验(RCT),该试验将超重/肥胖但无糖尿病的参与者随机分配至每周一次2.4mg皮下司马鲁肽,与安慰剂相比,随访时间至少为68周.主要结果是从基线到最长随访的相对体重变化。使用具有逆方差加权的随机效应模型以95％置信区间（CI）估计加权平均差（WMD）和相对风险（RR）。共纳入4个RCT（n=3,087）。在按类别提供BMI的3项试验中（n=2,783），94.0%的参与者基线BMI≥30kg/m2。与安慰剂相比，使用司马鲁肽与长期相对体重(WMD:-12.1%;95%CI-13.5,-10.7)和绝对体重(WMD:-12.3kg;95%CI-13.6,-11.0)显著下降相关.在最长的随访中，与安慰剂组的2.2%相比，33.4%的随机分组接受司马鲁肽组的体重下降≥20%(RR:15.08;95%CI9.31,24.43)。司马鲁肽参与者发生胃肠道不良事件的风险高于安慰剂组(RR:1:47;95%CI1.28,1.68);然而,这些事件大多数是短暂的，严重程度为轻度至中度，并且不需要停止治疗。总之,司马鲁肽对于超重/肥胖和无糖尿病的个体的持续体重减轻是有效的。
