Effects of SGLT2 Inhibitors on Cardiovascular and Lower Limb Events in Patients with Type 2 Diabetes: A Nationwide Population-Based Study.

IF 2.8 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Pub Date : 2025-03-28 eCollection Date: 2025-01-01 DOI:10.2147/DMSO.S515384

Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Yang Ho Kang, Joo Yeon Kim, Su Hyun Kim, Soo Yong Lee, Seung Hun Woo, Minae Park, Sojeong Park, Dong Hee Kim, Dasol Kang, Sujin Park, Dongwon Yi

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Abstract

Purpose: The cardiovascular (CV) benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) are well established, but their effects on lower limb events (LLEs) remain inconclusive, with conflicting findings from clinical trials and real-world studies. This study aimed to assess the risks of CV and LLEs associated with SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes.

Patients and methods: The study included patients with type 2 diabetes who were newly prescribed SGLT2i or DPP-4i using data from the National Health Insurance Service in South Korea. A 1:1 propensity score matching method was used to assign 97,584 patients to the SGLT2i and DPP-4i groups. The study endpoints included all-cause mortality, CV events, and LLEs-a composite outcome encompassing diabetic foot or ulcer, amputation, debridement, graft transplantation or flap operation, and revascularization.

Results: Over a median follow-up of 2.74 years, the SGLT2i group had a lower incidence of all-cause mortality (hazard ratio [HR] 0.63, 95% CI 0.51-0.78), heart failure (HR 0.85, 95% CI 0.78-0.93), ischemic stroke (HR 0.77, 95% CI 0.67-0.88), and peripheral artery disease (HR 0.66, 95% CI 0.63-0.69) than the DPP-4i group. However, no significant difference was observed in the incidence of myocardial infarction (HR 1.06, 95% CI 0.87-1.28) or LLEs (HR 1.05, 95% CI 0.80-1.38) between the two groups.

Conclusion: In this nationwide, real-world study, SGLT2i use demonstrated a neutral effect on LLEs compared to DPP-4i in patients with type 2 diabetes. However, SGLT2i was associated with a lower risk of all-cause mortality, heart failure, ischemic stroke, and peripheral artery disease. These findings contribute to the ongoing debate on the safety of SGLT2i regarding LLEs and highlight their broader CV benefits, warranting further investigation into their long-term effects on lower limb complications.

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SGLT2抑制剂对2型糖尿病患者心血管和下肢事件的影响：一项基于全国人群的研究

目的：钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）对心血管（CV）的益处已经确立，但其对下肢事件（LLEs）的影响仍不确定，临床试验和现实世界研究的结果相互矛盾。本研究旨在评估与二肽基肽酶-4抑制剂（DPP-4i）相比，2型糖尿病患者与SGLT2i相关的CV和LLEs的风险。患者和方法：该研究包括新开SGLT2i或DPP-4i处方的2型糖尿病患者，数据来自韩国国民健康保险服务。采用1:1倾向评分匹配方法将97,584例患者分配到SGLT2i和DPP-4i组。研究终点包括全因死亡率、心血管事件和lles，这是一个复合结局，包括糖尿病足或溃疡、截肢、清创、移植物移植或皮瓣手术和血运重建术。结果：中位随访2.74年，SGLT2i组的全因死亡率（风险比[HR] 0.63, 95% CI 0.51-0.78）、心力衰竭（HR 0.85, 95% CI 0.78-0.93）、缺血性卒中（HR 0.77, 95% CI 0.67-0.88）和外周动脉疾病（HR 0.66, 95% CI 0.63-0.69）的发生率低于DPP-4i组。然而，两组心肌梗死发生率（HR 1.06, 95% CI 0.87-1.28）或LLEs （HR 1.05, 95% CI 0.80-1.38）无显著差异。结论：在这项全国性的真实世界研究中，与DPP-4i相比，SGLT2i在2型糖尿病患者中对LLEs的作用中性。然而，SGLT2i与全因死亡率、心力衰竭、缺血性中风和外周动脉疾病的风险较低相关。这些发现有助于对SGLT2i治疗LLEs安全性的持续争论，并强调其更广泛的心血管益处，值得进一步研究其对下肢并发症的长期影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

5.90

自引率

6.10%

发文量

431

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.