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期刊来源：BMJ

原文链接：https://doi.org/10.1136/bmj-2023-076410

摘要内容如下：

客观

评价胰高血糖素样肽-1受体激动剂（GLP-1RAS）对成人2型糖尿病患者血糖控制、体重和血脂的疗效和安全性。

设计

系统综述和网络荟萃分析。

数据源

PubMed、Web of Science、Cochrane Central Register of Controlled Trials（CENTRAL）和EMBASE，从数据库开始到2023年8月19日。

选择研究的资格标准

符合条件的随机对照试验纳入了接受GLP-1Ra治疗的成人2型糖尿病患者，并与安慰剂或任何GLP-1Ra药物的疗效进行比较，随访时间至少为12周。采用交叉设计的试验、比较GLP-1ra和其他药物类别的非劣效性研究（无安慰剂组）、使用停药药物和非英语研究被视为不合格。

结果

76个合格试验，涉及15种GLP-1Ra药物，39246名受试者被纳入本网络荟萃分析。所有随后的估计都是指与安慰剂的比较。所有15个GLP-1RAS均有效降低血红蛋白A1c和空腹血糖浓度。Tirzepatide诱导血红蛋白A1c浓度的最大降低（平均差异-2.10%（95%置信区间-2.47%至-1.74%），累积等级曲线下表面94.2%；证据可信度高），空腹血糖浓度（-3.12 mmol/L（-3.59至-2.66），97.2%；高置信度），并证明是血糖控制最有效的GLP-1Ra药物。此外，GLP-1RAS被证明对2型糖尿病患者的体重管理有很大的益处。Cagrisema（Semaglutide与Cagrilintide）导致最高的体重减轻（平均差异-14.03 kg（95%置信区间-17.05至-11.00）；证据置信度高），其次是提尔西肽（-8.47 kg（-9.68至-7.26）；高置信度）。Semaglutide可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，该研究还提高了对GLP-1RAS引起的胃肠道不良事件的认识，尤其是对高剂量给药的安全性的关注。

结论

GLP-1RAS对治疗成人2型糖尿病有效。与安慰剂相比，Tirzepatide是通过降低血红蛋白A1c和空腹血糖浓度来控制血糖的最有效的GLP-1ra药物。GLP-1RAS还显著改善了2型糖尿病患者的体重管理，其中Cagrisema在减肥方面表现最好。该结果提示了GLP-1RAS的安全性问题，尤其是高剂量给药时的胃肠道不良事件。

系统评价注册

普洛斯彼罗CRD42022342845。

英文原文如下：

Abstracts

OBJECTIVE  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.

DESIGN  Systematic review and network meta-analysis.

DATA SOURCES  PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES  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a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible.

RESULTS  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 A1c and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A1c 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.

CONCLUSIONS  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 A1c 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.

SYSTEMATIC REVIEW REGISTRATION  PROSPERO CRD42022342845.

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