OBJECTIVE To compare the risk of composite peripheral artery disease (PAD) surgical outcome, including peripheral revascularization and amputation procedures, between new users of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP-4is). RESEARCH DESIGN AND METHODS This retrospective cohort study of U.S. veterans age ≥18 years with diabetes who received care from the Veterans Health Administration was performed from 1 October 2000 to 31 December 2021. Data were linked to Medicare, Medicaid, and the National Death Index. New use of SGLT2i or DPP-4i medications as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination was evaluated for an association with PAD surgical procedure for peripheral revascularization and amputation. A Cox proportional hazards model for time-to-PAD event analysis compared the risk of a PAD event between SGLT2is and DPP-4is in a propensity score–weighted cohort with a competing risk of death and allowance for events to occur up to 90 days or 360 days after stopping SGLT2is. RESULTS The weighted cohort included 76,072 SGLT2i vs. 75,833 DPP-4i use episodes. The median age was 69 years, HbA1c was 8.4% (interquartile range [IQR] 7.5–9.4%), and the median diabetes duration was 10.1 (IQR 6.6–14.6) years. There were 874 and 780 PAD events among SGLT2i and DPP-4i users, respectively, for an event rate of 11.2 (95% CI 10.5–11.9) and 10.0 (9.4–10.6) per 1,000 person-years (adjusted hazard ratio [aHR] 1.18 [95% CI 1.08–1.29]). When PAD events were allowed for 360 days after SGLT2i use ended, the aHR was 1.16 (95% CI 1.06–1.26). CONCLUSIONS SGLT2i as an add-on diabetes therapy was associated with an increased cause-specific hazard of PAD surgeries compared with DPP-4i.

中文翻译：

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使用 SGLT2i 与 DPP-4i 作为附加疗法和 PAD 相关手术事件（截肢、支架置入或血管手术）的风险：一项针对糖尿病退伍军人的队列研究


目的 比较钠-葡萄糖协同转运蛋白 2 抑制剂 （SGLT2is） 和二肽基肽酶 4 抑制剂 （DPP-4is） 新使用者之间复合外周动脉疾病 （PAD） 手术结局的风险，包括外周血运重建和截肢手术。研究设计和方法 这项回顾性队列研究于 2000 年 10 月 1 日至 2021 年 12 月 31 日对接受退伍军人健康管理局护理的 ≥18 岁糖尿病美国退伍军人进行。数据与 Medicare、Medicaid 和 National Death Index 相关联。评估新使用 SGLT2i 或 DPP-4i 药物作为二甲双胍、磺酰脲类药物或胰岛素单独或联合治疗的附加治疗与外周血运重建和截肢的 PAD 外科手术的相关性。用于 PAD 事件时间分析的 Cox 比例风险模型比较了倾向评分加权队列中 SGLT2is 和 DPP-4is 之间发生 PAD 事件的风险，该队列具有竞争性的死亡风险，并允许事件在停止 SGLT2is 后 90 天或 360 天内发生。结果加权队列包括 76,072 次 SGLT2i 和 75,833 次 DPP-4i 使用事件。中位年龄为 69 岁，HbA1c 为 8.4%（四分位距 [IQR] 7.5-9.4%），中位糖尿病病程为 10.1 （IQR 6.6-14.6） 年。SGLT2i 和 DPP-4i 用户中分别有 874 例和 780 例 PAD 事件，事件发生率为 11.2 （95% CI 10.5-11.9） 和 10.0 （9.4-10.6） / 1,000 人年 （调整后风险比 [aHR] 1.18 [95% CI 1.08-1.29]）。当 SGLT2i 使用结束后 360 天内允许 PAD 事件时，aHR 为 1.16 （95% CI 1.06–1.26）。结论与 DPP-4i 相比，SGLT2i 作为附加糖尿病疗法与 PAD 手术的病因特异性风险增加相关。