Comparative cardiovascular risk of sulfonylureas with low- and high-affinities for cardiac mitochondrial adenosine triphosphate-sensitive potassium channels versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: A cohort study.

IF 5.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2025-09-29 DOI:10.1111/dom.70157

Mei-Hsiu Chen, Liang-Yu Lin, Tung-Ying Hung, Tzu-Chieh Lin, Chia-Yu Li, Tzu-Han Lin, Yi-Hsuan Chen, Jun-Ting Liou, Meng-Ting Wang

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引用次数: 0

Abstract

Aims: To individually evaluate the cardiovascular safety of low- and high-affinity cardiac mitochondrial ATP-sensitive potassium (mitoK_ATP) channel sulfonylureas by comparing each to dipeptidyl peptidase-4 inhibitors (DPP-4i), a generally cardiovascular-neutral comparator, given prior evidence suggesting greater cardiovascular risk with high-affinity agents and the absence of a neutral active comparator.

Methods: A new user, active comparator cohort study using propensity score-based inverse probability of treatment weighting was conducted with Taiwan's nationwide claims database (2012-2022). Patients with recent pre-entry cardiovascular events were excluded. The primary outcome was 3-point major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, cardiovascular death); secondary outcomes included each MACE component and all-cause mortality.

Results: The study cohort included 466 158, 83 031, and 473 539 new users of low-affinity mitoK_ATP-channel sulfonylureas (gliclazide, glimepiride), high-affinity sulfonylureas (glyburide, glipizide), and DPP-4i, respectively (mean age, 60.2 years; 55.6% male). Compared with DPP-4i, low-affinity sulfonylureas were not associated with increased risks of 3-point MACE (Hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.96-1.06), cardiovascular death (HR, 1.01; 95% CI, 0.93-1.08), or all-cause mortality (HR, 0.97; 95% CI, 0.93-1.01). Conversely, high-affinity sulfonylureas were associated with 1.17-1.31-fold increased risks of 3-point MACE, cardiovascular death, and all-cause mortality.

Conclusions: Initiating low-affinity mitoK_ATP-channel sulfonylureas demonstrated cardiovascular safety comparable to DPP-4i, whereas high-affinity sulfonylureas were linked to increased cardiovascular risk and all-cause mortality. These findings suggest low-affinity sulfonylureas are a safer alternative to high-affinity agents and as safe as DPP-4i. They may be appropriate for individuals with diabetes when newer therapies are inaccessible or unnecessary.

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比较2型糖尿病患者心脏线粒体三磷酸腺苷敏感钾通道低亲和力和高亲和力磺脲类药物与二肽基肽酶-4抑制剂的心血管风险：一项队列研究

目的：考虑到先前的证据表明，高亲和性药物的心血管风险更大，且缺乏中性活性比较物，通过将低亲和性和高亲和性心脏线粒体atp敏感钾（mitoKATP）通道磺脲类药物与二肽基肽酶-4抑制剂（DPP-4i）进行比较，单独评估它们的心血管安全性。方法：利用台湾省全国理赔数据库（2012-2022），采用基于倾向得分的治疗加权逆概率进行了一项新的用户、主动比较者队列研究。排除近期有入院前心血管事件的患者。主要终点为3点主要不良心血管事件（MACE：缺血性卒中、心肌梗死、心血管性死亡）；次要结局包括MACE各组成部分和全因死亡率。结果：研究队列分别包括466 158、83 031和473 539名低亲和力mitokatp通道磺脲类药物（格列齐特、格列美脲）、高亲和力磺脲类药物（格列本脲、格列吡嗪）和DPP-4i的新使用者（平均年龄60.2岁，55.6%为男性）。与DPP-4i相比，低亲和力磺脲类药物与3点MACE（风险比[HR]， 1.01； 95%可信区间[CI]， 0.96-1.06）、心血管死亡（HR, 1.01; 95% CI, 0.93-1.08）或全因死亡率（HR, 0.97; 95% CI, 0.93-1.01）的风险增加无关。相反，高亲和性磺脲类药物与3点MACE、心血管死亡和全因死亡率增加1.17-1.31倍相关。结论：低亲和力mitokatp通道磺酰脲类药物的心血管安全性与DPP-4i相当，而高亲和力磺酰脲类药物与心血管风险和全因死亡率增加有关。这些发现表明，低亲和力磺脲类药物是一种比高亲和力药物更安全的替代品，与DPP-4i一样安全。当新的治疗方法无法获得或没有必要时，它们可能适用于糖尿病患者。

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, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.