Work

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

Year: 2025

Type: article

Abstract: AIMS: ) 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: -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: -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.

Source: Diabetes Obesity and Metabolism

DOI: 10.1111/dom.70157