■胰高血糖素样肽-1(GLP-1)受体激动剂(RA)在减轻体重方面对潜在危害的益处尚不清楚。这项研究旨在评估启动GLP-1RA与安慰剂对超重和肥胖但没有糖尿病的人减肥的利弊平衡。
■我们进行了利弊平衡建模,随着新证据的出现,它将被更新。我们在PubMed,对照试验登记处,药品审批和规范性文件,和截至2024年4月10日的结果偏好权重。我们使用成对荟萃分析来综合数据,以评估GLP-1RA的效果,从而为利害平衡模型提供信息。我们使用指数模型预测了1年和2年治疗期间正面和负面结果的绝对影响。我们对结果应用了偏好权重,范围从最不相关的0到最相关的1.0。然后,我们计算了实现5%和10%体重减轻的好处是否超过了普通规模的危害。这些分析解释了治疗效果的统计不确定性,偏好权重,和结果风险。
■我们包括8个RCT,涉及8847名参与者。合并的平均年龄为46.7岁,其中大多数是女性(74%)和肥胖者(96%)。在接受GLP-1RA治疗2年的1000人中,375(95%置信区间352至399)实现了10%的体重减轻,和318(296至339)与安慰剂治疗相比,体重减轻了5%。GLP-1RA组的一些损害结果更为常见,包括超过2年的每1000人41例腹痛事件(19至69例),胆石症(8,1至21),便秘(118,78至164),腹泻(100,42至173),脱发(57,10至176),低血糖(17,1至68),注射部位反应(4,-3至19),和呕吐(110,80至145)等。通过GLP-1RA治疗实现10%的体重减轻超过了累积的危害,第1年的净收益概率为0.97,第2年的净收益概率为0.91。绝对净收益相当于每1000人104(100至112),在2年内实现10%的体重减轻,而没有任何令人担忧的伤害。5%的体重减轻并没有显示净收益,在第1年和第2年的概率分别为0.13和0.01。然而,这些好处对偏好权重敏感,这表明,即使是5%的体重减轻也可能对那些不太担心伤害结果的人产生净益处。10%体重减轻的净收益是司马鲁肽最高的,其次是利拉鲁肽和替拉肽,2年概率分别为0.96、0.72和0.60。
■GLP-1RA的益处超过了治疗前2年对减肥的危害,然而,净获益取决于个人的治疗目标(10%或5%的体重减轻)和在追求体重减轻过程中接受危害的意愿.这意味着治疗决策必须针对个人进行个性化,以优化益处并减少危害和过度使用治疗。由于不同的证据,特别是关于跨研究的伤害结果,有必要不断更新和监测GLP-1RA的利弊平衡。
■SNSF和苏黎世环。
UNASSIGNED: The benefit of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) in weight reduction against potential harms remains unclear. This
study aimed at evaluating the benefit-harm balance of initiating GLP-1 RAs versus placebo for weight loss in people living with overweight and obesity but without diabetes.
UNASSIGNED: We performed benefit-harm balance modelling, which will be updated as new evidence emerges. We searched for randomised controlled trials (RCTs) in PubMed, controlled trials registry, drug approval and regulatory documents, and outcome preference weights as of April 10, 2024. We synthesize data using pairwise meta-analysis to estimate the effect of GLP-1 RAs to inform the benefit-harm balance modelling. We predicted the absolute effects of the positive and negative outcomes over 1 and 2 years of treatment using exponential models. We applied preference weights to the outcomes, ranging from 0 for least concerning to 1.0 for most concerning. We then calculated whether the benefit of achieving 5% and 10% weight loss outweighed the harms on a common scale. The analyses accounted for the statistical uncertainties of treatment effects, preference weights, and outcome risks.
UNASSIGNED: We included 8 RCTs involving 8847 participants. The pooled average age was 46.7 years, with the majority being women (74%) and people living with obesity (96%). Of 1000 persons treated with GLP-1 RAs for 2 years, 375 (95% confidence interval 352 to 399) achieved a 10% weight loss, and 318 (296 to 339) achieved a 5% weight loss compared to those treated with placebo. Several harm outcomes were more frequent in the GLP-1 RA group, including 41 abdominal pain events per 1000 persons over 2 years (19 to 69), cholelithiasis (8, 1 to 21), constipation (118, 78 to 164), diarrhoea (100, 42 to 173), alopecia (57, 10 to 176), hypoglycaemia (17, 1 to 68), injection site reactions (4, -3 to 19), and vomiting (110, 80 to 145) among others. Achieving a 10% weight loss with GLP-1 RA therapy outweighed the cumulative harms, with a net benefit probability of 0.97 at year 1 and 0.91 at year 2. The absolute net benefit was equivalent to 104 (100 to 112) per 1000 persons achieving a 10% weight loss over 2 years without experiencing any worrisome harm. A 5% weight loss did not show a net benefit, with probabilities of 0.13 and 0.01 at year 1 and year 2, respectively. However, these benefits were sensitive to preference weights, suggesting that even a 5% weight loss could be net beneficial for individuals with less concern about harm outcomes. The net benefit for a 10% weight loss was highest for semaglutide, followed by liraglutide and tirzepatide, with 2-year probabilities of 0.96, 0.72, and 0.60, respectively.
UNASSIGNED: The benefit of GLP-1 RAs exceeded the harms for weight loss in the first 2 years of treatment, yet the net benefit was dependent on individual\' treatment goals (10% or 5% weight loss) and willingness to accept harms in pursuit of weight loss. This implies that treatment decisions have to be personalized to individuals to optimize benefits and reduce harms and overuse of treatments. Due to varying evidence, especially regarding harm outcomes across studies, it is necessary to continuously update and monitor the benefit-harm balance of GLP-1 RAs.
UNASSIGNED: SNSF and LOOP Zurich.