近日，四川大学李舍予团队研究了一项成人2型糖尿病药物的系统评价和网络荟萃分析。2025年8月14日出版的《英国医学杂志》发表了这项成果。

为了提供关于成人2型糖尿病药物治疗的主要益处、危害和不确定性的最新证据，研究组进行了一项生活系统评价和网络元分析（NMA），使用频率随机效应和GRADE（分级推荐，评估，发展和评价）方法。计划每年至少更新两次。

数据源来自Medline和Embase，搜索到2024年7月31日的当前研究。研究选择至少24周的随机对照试验，将一种或多种药物与标准治疗、安慰剂或相互比较。共纳入869项试验（自2022年10月以来增加了53项试验），报告了13种药物类别（63种药物）的数据和26个感兴趣的结局。关于益处，中度至高度肯定的证据证实了钠-葡萄糖共转运体-2 （SGLT-2）抑制剂、胰高血糖素样肽-1受体激动剂（GLP-1RAs）和芬尼酮（最后一种用于确诊的慢性肾病患者）对心血管和肾脏的益处。

系统评价和NMA包括来自869项试验的493168名参与者（自2022年10月以来增加了53项试验），报告了13个药物类别（63种药物）和26个感兴趣结果的数据。关于益处，中度至高度确定的证据证实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-1RA）和finerenone（最后一种用于已确诊的慢性肾病患者）的心血管和肾脏益处。

减轻体重最有效的药物是替西帕肽（平均差异（MD）8.63kg（95%置信区间9.34至7.93）；中等确定性）和奥福利普龙（MD 7.87公斤（10.24至5.50）；低确定性），其次是其他八种GLP-1RA（高到中等确定性）。药物的绝对益处因心血管和肾脏结果的基线风险而异；使用交互式多重比较工具总结药物的风险分层绝对效应。关于药物特异性危害，SGLT-2抑制剂会增加生殖器感染（比值比（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），并可能增加截肢（OR 1.27（1.01至1.61）；适度确定性）；替西帕肽和GLP-1RA可能会增加严重的胃肠道事件（替西帕汀的风险增加最多（OR 4.21（1.87至9.49）；中等确定性））；finerenone会增加严重的高钾血症（OR 5.92（3.02至11.62）；高确定性）；噻唑烷二酮类药物会增加主要的骨质疏松性骨折，并可能增加心力衰竭的住院率。磺酰脲类、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。关于对其他糖尿病相关并发症（包括神经病变和视力障碍）的影响，有低到非常低的确定性证据。尽管人们对这个问题很感兴趣，但GLP-1RA是否可以减少痴呆症仍存在不确定性（OR 0.92（0.83至1.02）；低确定性）。

综上所述，这篇动态系统综述全面总结了药物对2型糖尿病成人患者的心血管、肾脏和减肥益处，以及药物特定的危害，包括SGLT-2抑制剂、GLP-1RA、finerenone和tirzepatide的影响。

附：英文原文

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

Author: Kailei Nong, Britta Tendal Jeppesen, Qingyang Shi, Thomas Agoritsas, Gordon H Guyatt, Heath White, Yiyuan Gao, Arnav Agarwal, Helen Macdonald, Xinyu Zou, Tanya Millard, Oliver Schnell, Nikolaus Marx, Frank C Brosius, Steve McDonald, Matthew Quigley, Xin Tian, Qinlin Fan, Barbara White, Yunhe Mao, Xiaohui Pan, Changhai Liu, Chunjuan Zhai, Chi Yuan, Qiang Li, Jing An, Yu Gan, Yanyan Wang, Yinghui Jin, Feng Sun, Zhiming Zhu, Lars Rydén, Eberhard Standl, Tari Turner, Per Olav Vandvik, Sheyu Li

Issue&Volume: 2025/08/14

Abstract:

Objective To provide up-to-date evidence on key benefits, harms, and uncertainties regarding medications for adults with type 2 diabetes.

Design Living systematic review and network meta-analysis (NMA), using frequentist random effects and GRADE (grading of recommendations, assessment, development and evaluation) approaches. Updates are planned at least two times a year.

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

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

Results The systematic review and NMA includes 493168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest. 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). 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). 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/#!/). 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. Sulfonylureas, insulin, and dipeptidyl peptidase-4 inhibitors probably increase the risk of severe hypoglycaemia. There is low to very low certainty evidence for effects on other diabetes-related complications, including neuropathy and visual impairment. 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).

Conclusions This living systematic review provides 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.

DOI: 10.1136/bmj-2024-083039

Source: https://www.bmj.com/content/390/bmj-2024-083039