Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis.

Methods

Living systematic reviewand network meta-analysis(NMA), using frequentist random effects and GRADE (grading of recommendations, assessment, development and evaluation) approaches.

采用频繁随机效应和GRADE（推荐分级的评估、制定与评价）方法进行活系统综述和网络荟萃分析（NMA）。

Updates are planned at least two times a year.

计划每年至少更新两次。

data_sources

Medline and Embase, searched up to 31 July 2024 for the current iteration.

在当前版本中，我们搜索了Medline和Embase数据库，直到2024年7月31日。

study_selection

Randomised controlled trials of at least 24 weeks comparing one or more medications with standard treatment, placebo, or each other.

至少24周的随机对照试验，比较一种或多种药物与标准治疗、安慰剂或彼此之间的效果。

Results

The systematic reviewand NMA includes 493 168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest.

系统评价和网络荟萃分析包括来自869项试验的493,168名参与者（自2022年10月以来新增53项试验），报告了13个药物类别（63种药物）和26个感兴趣的结果的数据。

Regarding benefits, moderate to high certainty evidence confirms the well established cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and finerenone (the last for patients with established chronic kidney disease).

关于益处，中到高确定性的证据确认了钠-葡萄糖共转运蛋白-2（SGLT-2）抑制剂、胰高血糖素样肽-1受体激动剂（GLP-1RAs）以及finerenone（适用于已确诊的慢性肾脏病患者）的心血管和肾脏益处。

The most effective drugs in reducing body weight were tirzepatide (mean difference (MD) -8.63 kg (95% confidence interval-9.34 to -7.93); moderate certainty) and orforglipron (MD -7.87 kg (-10.24 to -5.50); low certainty), followed by eight other GLP-1RAs (high to moderate certainty).

在减少体重方面最有效的药物是tirzepatide（平均差异（MD）-8.63公斤（95%置信区间-9.34至-7.93）；中等确定性）和orforglipron（MD -7.87公斤（-10.24至-5.50）；低确定性），其次是其他八种GLP-1RAs（高到中等确定性）。

Absolute benefits of medications vary substantially depending on the baseline risk of cardiovascular and kidney outcomes; risk-stratified absolute effects of medications are summarised using an interactive multiple comparisons tool (https://matchit.magicevidence.org/250709dist-diabetes/#!/).

药物的绝对益处根据心血管和肾脏结果的基线风险而显著不同；使用交互式多重比较工具（https://matchit.magicevidence.org/250709dist-diabetes/#!/）总结了按风险分层的药物绝对效果。

Regarding medication-specific harms, SGLT-2 inhibitors increase genital infections (odds ratio (OR) 3.29 (95% CI 2.88 to 3.77); high certainty) and ketoacidosis due to diabetes (OR 2.08 (1.45 to 2.99); high certainty), and probably increase amputations (OR 1.27 (1.01 to 1.61); moderate certainty); tirzepatide and GLP-1RAs probably increase severe gastrointestinal events (most increased risk with tirzepatide (OR 4.21 (1.87 to 9.49); moderate certainty)); finerenone increases severe hyperkalaemia (OR 5.92 (3.02 to 11.62); high certainty); and thiazolidinediones increase major osteoporotic fractures and probably increase hospitalisation for heart failure.

关于药物特定的不良事件，SGLT-2抑制剂增加了生殖器感染（优势比（OR）3.29（95% CI 2.88至3.77）；高确定性）和糖尿病引起的酮症酸中毒（OR 2.08（1.45至2.99）；高确定性），并且可能增加截肢（OR 1.27（1.01至1.61）；中等确定性）；tirzepatide和GLP-1RAs可能增加严重胃肠道事件（tirzepatide风险最高（OR 4.21（1.87至9.49）；中等确定性））；finerenone增加了严重高钾血症（OR 5.92（3.02至11.62）；高确定性）；噻唑烷二酮增加了主要骨质疏松性骨折，并可能增加因心力衰竭住院。

Sulfonylureas, insulin, and dipeptidyl peptidase-4 inhibitors probably increase the risk of severe hypoglycaemia.

磺脲类药物、胰岛素和二肽基肽酶-4抑制剂可能会增加严重低血糖的风险。

There is low to very low certainty evidence for effects on other diabetes-related complications, including neuropathy and visual impairment.

对于其他糖尿病相关并发症（包括神经病变和视力损害）的影响，证据的确定性较低至非常低。

Despite interest in the issue, there is uncertainty about whether GLP-1RAs may reduce dementia (OR 0.92 (0.83 to 1.02); low certainty).

尽管对这个问题很感兴趣，但尚不确定GLP-1RAs是否可以降低痴呆的发生率（OR 0.92（0.83至1.02）；低确定性）。

Conclusions

This living systematic reviewprovides a comprehensive summary of the cardiovascular, kidney, and weight loss benefits, as well as medication-specific harms of medications for adults with type 2 diabetes, including effects of SGLT-2 inhibitors, GLP-1RAs, finerenone and tirzepatide.

这项活系统综述为2型糖尿病成人患者提供了关于心血管、肾脏和减重益处以及药物特定危害的全面总结，包括SGLT-2抑制剂、GLP-1RAs、finerenone和tirzepatide的效果。

systematic_review_registration

PROSPERO number: CRD42022325948.

PROSPERO编号：CRD42022325948。

A more detailed protocol is available at https://data.aliveevidence.org/records/q02rv-km486.

更详细的方案可在https://data.aliveevidence.org/records/q02rv-km486.获取。

READERS' NOTES: This article is the first version of a living systematic review.

读者须知：本文是活系统综述的首个版本。

It is linked to a living BMJ Rapid Recommendation and other living clinical practice guidelines, presenting risk stratified recommendations for patients with type 2 diabetes at lower, moderate, and higher risk of cardiovascular and kidney complications.

它与活的BMJ快速推荐和其他活的临床实践指南相关联，为2型糖尿病患者提供心血管和肾脏并发症低、中、高风险分层的建议。

The latest evidence will be made available via the BMJ Rapid Recommendation and via an interactive GRADE evidence summary (MATCH-IT: https://matchit.magicevidence.org/250709dist-diabetes/#!/).

最新的证据将通过BMJ快速推荐和交互式GRADE证据摘要(MATCH-IT: https://matchit.magicevidence.org/250709dist-diabetes/#!/)提供。

Major updates will be published in The BMJ.

主要更新将在《英国医学杂志》(The BMJ)上发表。