Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, U.K.
Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, U.K.
Diabetes Care. 2022 Apr 1;45(4):909-918. doi: 10.2337/dc21-1113.
To assess associations between current use of sodium-glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and their combination and risk for major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) in people with type 2 diabetes.
In three nested case-control studies involving patients with type 2 diabetes in England and Wales (primary care data from the Clinical Practice Research Datalink and Secure Anonymised Information Linkage Databank with linkage to hospital and mortality records), we matched each patient experiencing an event with up to 20 control subjects. Adjusted odds ratios (ORs) for MACCE and HF among patients receiving SGLT2i or GLP-1RA regimens versus other combinations were estimated using conditional logistic regression and pooled using random-effects meta-analysis.
Among 336,334 people with type 2 diabetes and without cardiovascular disease, 18,531 (5.5%) experienced a MACCE. In a cohort of 411,206 with type 2 diabetes and without HF, 17,451 (4.2%) experienced an HF event. Compared with other combination regimens, the adjusted pooled OR and 95% CI for MACCE associated with SGLT2i regimens was 0.82 (0.73, 0.92), with GLP-1RA regimens 0.93 (0.81, 1.06), and with the SGLT2i/GLP-1RA combination 0.70 (0.50, 0.98). Corresponding data for HF were SGLT2i 0.49 (0.42, 0.58), GLP-1RA 0.82 (0.71, 0.95), and SGLT2i/GLP-1RA combination 0.43 (0.28, 0.64).
SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in primary prevention of MACCE and HF and GLP-1RA for HF. These data call for primary prevention trials using these agents and their combination.
评估钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）、胰高血糖素样肽 1 受体激动剂（GLP-1RA）及其联合治疗与 2 型糖尿病患者主要不良心脏和脑血管事件（MACCE）和心力衰竭（HF）风险之间的关联。
在三项嵌套病例对照研究中，我们纳入了英格兰和威尔士的 2 型糖尿病患者（来自临床实践研究数据链接和安全匿名信息链接数据库的初级保健数据，并与医院和死亡率记录链接），将每个发生事件的患者与最多 20 名对照患者进行匹配。使用条件逻辑回归估计接受 SGLT2i 或 GLP-1RA 治疗方案与其他联合治疗方案的患者中 MACCE 和 HF 的调整比值比（OR），并使用随机效应荟萃分析进行汇总。
在 336334 名无心血管疾病的 2 型糖尿病患者中，有 18531 人（5.5%）发生了 MACCE。在一个 411206 名无 HF 的 2 型糖尿病患者队列中，有 17451 人（4.2%）发生了 HF 事件。与其他联合治疗方案相比，SGLT2i 治疗方案与 MACCE 相关的调整后汇总 OR 和 95%CI 为 0.82（0.73，0.92），GLP-1RA 治疗方案为 0.93（0.81，1.06），SGLT2i/GLP-1RA 联合治疗方案为 0.70（0.50，0.98）。HF 的相应数据为 SGLT2i 为 0.49（0.42，0.58），GLP-1RA 为 0.82（0.71，0.95），SGLT2i/GLP-1RA 联合治疗方案为 0.43（0.28，0.64）。
SGLT2i 和 SGLT2i/GLP-1RA 联合治疗方案可能有益于 MACCE 和 HF 的一级预防，GLP-1RA 可能有益于 HF 的治疗。这些数据呼吁使用这些药物及其联合进行一级预防试验。
