Yao Haiqiang, Zhang Anqi, Li Delong, Wu Yuqi, Wang Chong-Zhi, Wan Jin-Yi, Yuan Chun-Su
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China.
BMJ. 2024 Jan 29;384:e076410. doi: 10.1136/bmj-2023-076410.
To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes.
Systematic review and network meta-analysis.
PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023.
Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible.
76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration.
GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events.
PROSPERO CRD42022342845.
评估胰高血糖素样肽-1受体激动剂（GLP-1RAs）对2型糖尿病成人患者血糖控制、体重和血脂水平的比较疗效及安全性。
系统评价和网状Meta分析。
从数据库建立至2023年8月19日的PubMed、科学网、Cochrane对照试验中心注册库（CENTRAL）和Embase。
符合条件的随机对照试验纳入接受GLP-1RA治疗的2型糖尿病成人患者，并将其疗效与安慰剂或任何GLP-1RA药物进行比较，随访时间至少12周。交叉设计试验、比较GLP-1RA与其他药物类别且无安慰剂组的非劣效性研究、使用撤市药物的研究以及非英文研究均被视为不符合条件。
该网状Meta分析纳入了76项符合条件的试验，涉及15种GLP-1RA药物和39246名参与者；所有后续估计值均指与安慰剂的比较。所有15种GLP-1RAs均有效降低糖化血红蛋白和空腹血糖浓度。替尔泊肽使糖化血红蛋白浓度降低幅度最大（平均差值-2.10%（95%置信区间-2.47%至-1.74%），累积排序曲线下面积94.2%；证据可信度高），空腹血糖浓度降低幅度也最大（-3.12 mmol/L（-3.59至-2.66），97.2%；证据可信度高），是控制血糖最有效的GLP-1RA药物。此外，GLP-1RAs对2型糖尿病患者的体重管理有显著益处。卡格列净司美格鲁肽（司美格鲁肽与卡格列净联用）导致体重减轻最多（平均差值-14.03 kg（95%置信区间-17.05至-11.00）；证据可信度高），其次是替尔泊肽（-8.47 kg（-9.68至-7.26）；证据可信度高）。司美格鲁肽有效降低低密度脂蛋白浓度（-0.16 mmol/L（-0.30至-0.02））和总胆固醇浓度（-0.48 mmol/L（-0.84至-0.11））。此外，本研究还提高了对GLP-1RAs所致胃肠道不良事件的认识，高剂量给药时尤其需要关注安全性。
GLP-1RAs对治疗2型糖尿病成人患者有效。与安慰剂相比，替尔泊肽通过降低糖化血红蛋白和空腹血糖浓度，是控制血糖最有效的GLP-1RA药物。GLP-1RAs还显著改善了2型糖尿病患者的体重管理，卡格列净司美格鲁肽在体重减轻方面表现最佳。结果提示GLP-1RAs存在安全性问题，尤其是高剂量给药时的胃肠道不良事件。
PROSPERO CRD42022342845
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