(043) Concomitant Use of Sulfonylurea and Amiodarone Associated with the Risk of Severe Hypoglycemia

Background: Despite the remarkable therapeutic effects of amiodarone in rhythm control, it is crucial to recognize its biological mechanism of CYP2C9 inhibition, as it may lead to the induction of CYP2C9-mediated drug-drug interactions. Moreover, considering type 2 diabetes as an independent risk factor for atrial fibrillation, the co-administration of sulfonylurea and amiodarone is frequently encountered in routine clinical settings, warranting careful attention to potential clinical implications and safety concerns in such patient populations.

Objectives: To evaluate the risk of severe hypoglycemia associated with concomitant use of sulfonylurea and amiodarone among patients with type 2 diabetes and atrial fibrillation.

Methods: This retrospective cohort study utilized the Korea National Health database from 2010 to 2022, encompassing patients with type 2 diabetes and atrial fibrillation. Concomitant use was defined as initiating amiodarone or other antiarrhythmics (flecainide, sotalol, propafenone) while on sulfonylurea treatment. Outcomes included severe hypoglycemia, comprising the composite outcomes of hospitalization or ER visit for hypoglycemia. Patients were followed from the initiation of antiarrhythmic medication with sulfonylurea to the earliest outcome, discontinuation of study drugs (antiarrhythmic medication or sulfonylurea), switch, death, or study end (31 Dec 2022), adopting a 30-day grace period for discontinuation measurement. 1:1 propensity score matching was conducted for confounding control, employing Poisson models for incidence rates and rate differences. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CIs). Secondary analyses involved cohort stratification by age, sex, history of insulin use, and history of heart failure.

Results: After 1:1 PS matching, 11,365 patient pairs were identified. The concomitant use of amiodarone and sulfonylurea was associated with an elevated risk of severe hypoglycemia compared with the concomitant use of other antiarrhythmics and sulfonylurea (HR 1.70, 95% CI 1.27-2.29). Female patients (2.08, 1.41-3.06) and patients aged 65 years or older (2.05, 1.45-2.89) showed a greater risk of severe hypoglycemia. However, patients with a history of insulin use (1.38, 0.85-2.54) and a history of heart failure (1.27, 0.54-2.99) did not show an increased risk of severe hypoglycemia.

Conclusions: The potential risk of severe hypoglycemia increases when amiodarone is concomitantly used with sulfonylurea among patients with type 2 diabetes and atrial fibrillation. The findings of this study suggest that it is important to take into account the risk of severe hypoglycemia when managing rhythm control medications in patients with type 2 diabetes.