Vosoughi Kia, Atieh Jessica, Khanna Lehar, Khoshbin Katayoun, Prokop Larry J, Davitkov Perica, Murad M Hassan, Camilleri Michael
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN.
Library-Public Service Department, Mayo Clinic, Rochester, MN.
EClinicalMedicine. 2021 Nov 27;42:101213. doi: 10.1016/j.eclinm.2021.101213. eCollection 2021 Dec.
Comparative effectiveness of 7 glucagon-like peptide 1 (GLP-1) agents on weight loss (WL) in obesity remains unknown.
We performed a systematic review, network meta-analysis (NMA) utilizing the following data sources: MEDLINE, EMBASE, Scopus, Cochrane Central and clinical trial registries, from inception to March 2, 2021. The prespecified criteria for study inclusion were randomized clinical trials (RCTs) of ≥12 weeks' duration. The data appraisal and extraction were performed by two investigators independently, using the published reports. The main outcomes and statistical methods were weight loss over placebo (WLOP) and adverse events (AEs) among GLP-1 agents using random-effects NMA (frequentist approach); relative ranking using surface under the cumulative ranking (SUCRA) method and certainty of evidence using grading of recommendations, assessment, development and evaluations (GRADE).
64 RCTs (from 2004 to 2021) included 27018 patients (median of age, 55.1 years old; 57.4% women; baseline weight 94.8kg and BMI 33.0kg/m; trial duration 26 weeks). Direct meta-analysis showed significant WLOP with: -1.44kg (95% CI, -2.14 to -0.74) with dulaglutide ≥1.5 mg; -1.82kg (-2.42 to -1.23) with exenatide immediate release (IR); -2.20kg (-4.31 to -0.08) with exenatide extended release (ER); -3.20kg (-6.53 to 0.15) with efpeglenatide; -2.72kg (-3.35 to -2.09) with liraglutide ≤1.8mg; -4.49kg (-5.26 to -3.72) with liraglutide >1.8mg; -0.62kg (-1.22 to -0.02) with lixisenatide; -4.33kg (-5.71 to -3.00) with semaglutide SQ <2.4mg; -9.88kg (-13.17 to -6.59) with semaglutide SQ 2.4mg; -2.73kg (-4.81 to -0.65) with semaglutide oral; and -1.71kg (-2.64 to -0.78) with taspoglutide. Highest WLOP were with semaglutide SQ 2.4mg and <2.4mg, and liraglutide >1.8mg (SUCRAs 100, 86.1, 82.8 respectively). Highest SUCRAs for discontinuation due to AEs were with taspoglutide and liraglutide >1.8mg. Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%). Heterogeneity (I >50%) in WL and AEs reflected magnitude, not direction of effect.
7种胰高血糖素样肽1（GLP-1）药物在肥胖症体重减轻（WL）方面的比较疗效尚不清楚。
我们进行了一项系统评价和网络荟萃分析（NMA），利用以下数据来源：MEDLINE、EMBASE、Scopus、Cochrane中心和临床试验注册库，时间范围从开始到2021年3月2日。预先设定的研究纳入标准为持续时间≥12周的随机临床试验（RCT）。数据评估和提取由两名研究人员独立进行，使用已发表的报告。主要结局和统计方法包括使用随机效应NMA（频率学派方法）比较GLP-1药物相对于安慰剂的体重减轻（WLOP）和不良事件（AE）；使用累积排名曲线下面积（SUCRA）方法进行相对排名，以及使用推荐分级、评估、制定与评价（GRADE）方法评估证据的确定性。
64项RCT（2004年至2021年）纳入了27018名患者（年龄中位数为55.1岁；女性占57.4%；基线体重94.8kg，BMI为33.0kg/m²；试验持续时间26周）。直接荟萃分析显示，以下药物的WLOP具有统计学意义：度拉糖肽≥1.5mg时为-1.44kg（95%CI，-2.14至-0.74）；艾塞那肽速释（IR）为-1.82kg（-2.42至-1.23）；艾塞那肽缓释（ER）为-2.20kg（-4.31至-0.08）；依帕列净肽为-3.20kg（-6.53至0.15）；利拉鲁肽≤1.8mg时为-2.72kg（-3.35至-2.09）；利拉鲁肽>1.8mg时为-4.49kg（-5.26至-3.72）；利司那肽为-0.62kg（-1.22至-0.02）；司美格鲁肽皮下注射<2.4mg时为-4.33kg（-5.71至-3.00）；司美格鲁肽皮下注射2.4mg时为-9.88kg（-13.17至-6.59）；司美格鲁肽口服制剂为-2.73kg（-4.81至-0.65）；替西帕肽为-1.71kg（-2.64至-0.78）。WLOP最高的是司美格鲁肽皮下注射2.4mg、<2.4mg以及利拉鲁肽>1.8mg（SUCRA分别为100、86.1、82.8）。因AE导致停药的SUCRA最高的是替西帕肽和利拉鲁肽>1.8mg。随机序列生成（29.7%）、分配隐藏（26.6%）和结局数据不完整（26.6%）方面的偏倚风险较高或不明确。WL和AE方面的异质性（I²>50%）反映的是效应的大小，而非方向。
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