超越胰高血糖素样肽-1：双重和三重肠促胰岛素激动剂在2型糖尿病个性化治疗中的疗效和安全性——一项系统评价与网状Meta分析

Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care-a systematic review and network meta-analysis.

作者信息

Yan Kangling, Yu Haichuan, Blaise Benoît

机构信息

School of Medical Sciences - Faculty of Medicine and Health, University of Sydney, City Road, Sydney, NSW, 2006, Australia.

Wuhan University, Wuhan City, 430061, Hubei, China.

出版信息

Acta Diabetol. 2025 Jun 5. doi: 10.1007/s00592-025-02534-y.

BACKGROUND

Dual and triple incretin-based agonists, targeting combinations of GLP-1, GIP, and glucagon receptors, represent an innovative approach in T2DM care. However, comparative efficacy and safety analyses tailored to receptor-specific strategies are limited.

PURPOSE

This systematic review and network meta-analysis uniquely evaluates the efficacy and safety of dual and triple incretin agonists compared to standard therapies, offering insights into personalized, receptor-specific T2DM therapies.

DATA SOURCES

Systematic searches in PubMed, Web of Science, Cochrane Library, and Embase (up to July 2024) identified RCTs.

STUDY SELECTION

Trials assessing dual or triple incretin therapies in T2DM with outcomes on weight, HbA1c, FBG, AEs, and SAEs were included.

DATA EXTRACTION

Data on efficacy and safety were extracted by independent reviewers and assessed for quality using the NIH Quality Assessment Tool.

DATA SYNTHESIS

Retatrutide achieved the greatest weight reduction (MD: - 8.601; 95% CrI: - 11.20 to - 5.95) while Tirzepatide was most effective in lowering FBG (MD: - 57.30) and HbA1c ( - 1.88), with 95% CrIs of - 65.41 to - 48.9 and - 2.15 to - 1.64 respectively. Tirzepatide (RR 1.15) and Cotadutide (1.38) increased AEs, while Semaglutide reduced SAEs (0.35); 95% Crls: 1.04-1.33, 1.16-1.68, and 0.13-0.78, respectively.

LIMITATIONS

Small sample sizes, short study durations, and reliance on indirect comparisons in some cases may limit the certainty of these findings. Direct head-to-head trials are needed to confirm these results.

CONCLUSION

Receptor-specific targeting optimizes T2DM treatment, with Semaglutide supporting glycemic control, Tirzepatide enhancing weight loss and glucose regulation, and Retatrutide potentially offering broader metabolic benefits, advancing receptor-targeted, personalized therapy.

PROSPERO REGISTRATION NUMBER

CRD42024532368.

背景

基于双重和三重肠促胰岛素的激动剂，靶向胰高血糖素样肽-1（GLP-1）、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素受体的组合，代表了2型糖尿病（T2DM）治疗中的一种创新方法。然而，针对受体特异性策略的疗效和安全性比较分析有限。

目的

本系统评价和网状Meta分析独特地评估了双重和三重肠促胰岛素激动剂与标准疗法相比的疗效和安全性，为个性化、受体特异性的T2DM治疗提供见解。

数据来源

在PubMed、科学网、Cochrane图书馆和Embase（截至2024年7月）进行系统检索，以识别随机对照试验（RCT）。

研究选择

纳入评估T2DM双重或三重肠促胰岛素疗法对体重、糖化血红蛋白（HbA1c）、空腹血糖（FBG）、不良事件（AE）和严重不良事件（SAE）影响的试验。

数据提取

由独立评审员提取疗效和安全性数据，并使用美国国立卫生研究院质量评估工具评估质量。

数据合成

瑞他鲁肽实现了最大程度的体重减轻（平均差：-8.601；95%可信区间：-11.20至-5.95），而替尔泊肽在降低FBG（平均差：-57.30）和HbA1c（-1.88）方面最有效，95%可信区间分别为-65.41至-48.9和-2.15至-1.64。替尔泊肽（相对风险1.15）和可他肽（1.38）增加了AE，而司美格鲁肽降低了SAE（0.35）；95%可信区间分别为1.04 - 1.33、1.16 - 1.68和0.13 - 0.78。

局限性

样本量小、研究持续时间短以及在某些情况下依赖间接比较可能会限制这些发现的确定性。需要直接的头对头试验来证实这些结果。

结论

受体特异性靶向优化了T2DM治疗，司美格鲁肽有助于血糖控制，替尔泊肽增强体重减轻和血糖调节，瑞他鲁肽可能带来更广泛的代谢益处，推动了受体靶向的个性化治疗。

PROSPERO注册号：CRD42024532368。