Teo Yao Neng, Ting Adriel Z H, Teo Yao Hao, Chong Elliot Yeung, Tan Joshua Teik Ann, Syn Nicholas L, Chia Alys Z Q, Ong How Ting, Cheong Alex Jia Yang, Li Tony Yi-Wei, Poh Kian Keong, Yeo Tiong Cheng, Chan Mark Yan-Yee, Wong Raymond C C, Chai Ping, Sia Ching-Hui
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore.
Am J Cardiovasc Drugs. 2022 May;22(3):299-323. doi: 10.1007/s40256-022-00528-7. Epub 2022 Mar 22.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-hyperglycemic drugs that has been steadily increasing in popularity due to its cardiovascular and renal benefits. Dual SGLT1/SGLT2 (SGLT1/2) inhibitors have potentially augmented anti-hyperglycemic action due to additional SGLT1 inhibition. This network meta-analysis aimed to compare the treatment effect across various outcomes between pure SGLT2 inhibitors and combined SGLT1/2 inhibitors in patients with diabetes.
Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for randomized controlled trials published from inception to 15th January 2022. Frequentist network meta-analysis was conducted to summarize the treatment effects reported in individual trials, stratified by type 1 (T1DM) and type 2 diabetes mellitus (T2DM). This meta-analysis was registered on PROSPERO (CRD42020222031).
Our meta-analysis included 111 articles, comprising a combined cohort of 103,922 patients. SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, and luseogliflozin) and SGLT1/2 inhibitors (licogliflozin and sotagliflozin) were compared. Frequentist network meta-analysis demonstrated that in T2DM patients, SGLT1/2 inhibitors led to a decreased hazard rate of myocardial infarction (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.56-0.98) and stroke (HR 0.65, 95% CI 0.47-0.92) compared with SGLT2 inhibitors. SGLT2 inhibitors achieved a greater hemoglobin A1c (HbA1c) reduction than SGLT1/2 inhibitors (0.16%, 95% CI 0.06-0.26). In patients with T2DM, the risk of diarrhea (risk ratio [RR] 1.42, 95% CI 1.07-1.88) and severe hypoglycemia (RR 5.89, 95% CI 1.41-24.57) were found to be higher with SGLT1/2 inhibitor use compared with SGLT2 inhibitor use. No differences were observed for cardiovascular, metabolic, and safety outcomes between SGLT1/2 inhibitors and SGLT2 inhibitors in patients with T1DM.
In patients with T2DM, compared with pure SGLT2 inhibitors, combined SGLT1/2 inhibitors demonstrated a lower risk of myocardial infarction and of stroke, but were associated with a higher risk of diarrhea and severe hypoglycemia.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是一类抗高血糖药物，因其对心血管和肾脏的益处而越来越受欢迎。双重SGLT1/SGLT2（SGLT1/2）抑制剂由于对SGLT1的额外抑制作用，可能增强抗高血糖作用。这项网状荟萃分析旨在比较糖尿病患者中单纯SGLT2抑制剂与联合SGLT1/2抑制剂在各种结局方面的治疗效果。
检索了四个电子数据库（PubMed、Embase、Cochrane和Scopus），以查找从数据库建立至2022年1月15日发表的随机对照试验。进行了频率学派网状荟萃分析，以汇总各单项试验报告的治疗效果，并按1型糖尿病（T1DM）和2型糖尿病（T2DM）进行分层。这项荟萃分析已在国际前瞻性系统评价注册库（PROSPERO，注册号：CRD42020222031）注册。
我们的荟萃分析纳入了111篇文章，共涉及103,922名患者。比较了SGLT2抑制剂（达格列净、恩格列净、卡格列净、依帕列净、艾托格列净和鲁格列净）和SGLT1/2抑制剂（利司那格列净和索格列净）。频率学派网状荟萃分析表明，在T2DM患者中，与SGLT2抑制剂相比，SGLT1/2抑制剂导致心肌梗死的风险比（HR）降低（HR 0.74，95%置信区间[CI] 0.56-0.98），中风风险也降低（HR 0.65，95% CI 0.47-0.92）。SGLT2抑制剂比SGLT1/2抑制剂能使糖化血红蛋白（HbA1c）降低更多（降低0.16%，95% CI 0.06-0.26）。在T2DM患者中，发现使用SGLT1/2抑制剂时腹泻风险（风险比[RR] 1.42，95% CI 1.07-1.88）和严重低血糖风险（RR 5.89，95% CI 1.41-24.57）高于使用SGLT2抑制剂。在T1DM患者中，未观察到SGLT1/2抑制剂与SGLT2抑制剂在心血管、代谢和安全性结局方面存在差异。
在T2DM患者中，与单纯SGLT2抑制剂相比，联合SGLT1/2抑制剂显示出较低的心肌梗死和中风风险，但与较高的腹泻和严重低血糖风险相关。
