Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montréal, Québec, Canada.
Division of Endocrinology, Department of Medicine, Jewish General Hospital, Montréal, Québec, Canada.
Diabetes Care. 2020 Oct;43(10):2444-2452. doi: 10.2337/dc20-0267. Epub 2020 Aug 5.
Reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes.
This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results.
The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71-1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule.
In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects.
与钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂相关的截肢报告结果并不一致。我们旨在比较 2 型糖尿病患者使用 SGLT2 抑制剂与使用二肽基肽酶 4（DPP-4）抑制剂的情况下，发生膝下截肢的风险。
本多中心观察性研究使用了来自加拿大 7 个省和英国的行政医疗保健数据库。采用基于现患患者的新用户设计和时间条件倾向评分，将 SGLT2 抑制剂的新使用者与 DPP-4 抑制剂的新使用者相匹配。使用 Cox 比例风险模型来估计 SGLT2 抑制剂与 DPP-4 抑制剂使用者的特定部位调整后的风险比（HR）和相应的 95%CI，以评估膝下截肢的发生率。使用随机效应荟萃分析来汇总特定部位的结果。
该研究队列包括 207817 例 SGLT2 抑制剂的新使用者，与 207817 例 DPP-4 抑制剂的新使用者相匹配。在平均 11 个月的暴露随访时间内，SGLT2 抑制剂使用者的截肢率为每 1000 人年 1.3 例，DPP-4 抑制剂使用者的截肢率为每 1000 人年 1.5 例。与 DPP-4 抑制剂相比，SGLT2 抑制剂使用者发生膝下截肢的调整 HR 为 0.88（95%CI 0.71-1.09）。在按特定 SGLT2 抑制剂分子进行的分层分析中，也得到了类似的结果。
在这项大型多中心观察性研究中，与使用 DPP-4 抑制剂相比，2 型糖尿病患者使用 SGLT2 抑制剂与发生膝下截肢之间没有关联。尽管这些发现提供了一些保证，但仍需要进行随访时间更长的研究来评估潜在的长期影响。
