{"title":"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","authors":"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","doi":"10.1111/dom.70157","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>To individually evaluate the cardiovascular safety of low- and high-affinity cardiac mitochondrial ATP-sensitive potassium (mitoK<sub>ATP</sub>) 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The study cohort included 466 158, 83 031, and 473 539 new users of low-affinity mitoK<sub>ATP</sub>-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.</p><p><strong>Conclusions: </strong>Initiating low-affinity mitoK<sub>ATP</sub>-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.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1111/dom.70157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>To individually evaluate the cardiovascular safety of low- and high-affinity cardiac mitochondrial ATP-sensitive potassium (mitoK<sub>ATP</sub>) 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The study cohort included 466 158, 83 031, and 473 539 new users of low-affinity mitoK<sub>ATP</sub>-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.</p><p><strong>Conclusions: </strong>Initiating low-affinity mitoK<sub>ATP</sub>-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.</p>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/dom.70157\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.70157","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
Aims: To individually evaluate the cardiovascular safety of low- and high-affinity cardiac mitochondrial ATP-sensitive potassium (mitoKATP) 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 mitoKATP-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 mitoKATP-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.
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.
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