Association Between Specificity of Sulfonylureas to Cardiac Mitochondrial KATP Channels and the Risk of Major Adverse Cardiovascular Events in Type 2 Diabetes
RESEARCH DESIGN AND METHODS: Using the Taiwan nationwide healthcare claims database, patients with type 2 diabetes initiating sulfonylurea monotherapy between 2007 and 2016 were included in the cohort study. 33,727 new mitoKATP channel-high affinity (glyburide and glipizide) and low affinity (gliclazide and glimepiride) sulfonylurea users, respectively, were identified after 1:1 propensity score matching. Cox proportional hazard models were used to estimate adjusted hazard ratio (aHRs) and 95% confidence interval (CI).
RESULTS: MitoKATP channel-high affinity sulfonylureas were associated with a significantly increased risk of three-point MACEs (aHR, 1.21 [95% CI, 1.03–1.44]), ischemic stroke (aHR, 1.23 [95% CI, 1.02-1.50]), and cardiovascular death (aHR, 2.61 [95% CI, 1.31–5.20]) but not with that of MI (aHR, 1.04 [95% CI, 0.75-1.46]). The duration-response analyses revealed the highest MACE risk to be within 90 days of therapy (aHR, 4.67 [95% CI, 3.61-6.06]).
CONCLUSIONS: Cardiac mitoKATP channel-high affinity sulfonylureas were associated with an increased MACE risk compared with low affinity sulfonylureas in a nationwide population with diabetes.