Risk of Severe Hypoglycemia Associated With Concomitant Use of Sulfonylureas and Amiodarone

To evaluate whether initiation of amiodarone while receiving sulfonylurea is associated with an increased risk of severe hypoglycemia compared with the initiation of other antiarrhythmic agents (flecainide, sotalol, or propafenone) while receiving sulfonylurea.

We conducted a population-based cohort study using South Korean National Health Insurance Service claims data from 2010 to 2022. Adults aged 18 years or older with type 2 diabetes who initiated oral antiarrhythmic therapy (amiodarone or comparator agents) while on sulfonylurea treatment between 1 January 2011 and 31 December 2022, were included. The first dispensing date of an antiarrhythmic agent while on sulfonylureas was the index date. Patients with prior use of first-generation sulfonylureas, meglitinides, insulin, or antiarrhythmics, or those initiating multiple antiarrhythmic drugs on the index date were excluded. The primary outcome was severe hypoglycemia, defined as hospital admission or emergency department visits with a primary diagnosis of hypoglycemia. Propensity score overlap weighting and weighted Cox models were applied.

Among 12 730 eligible patients, 5325 (41.8%) initiated amiodarone and 7405 (58.2%) initiated comparator antiarrhythmics. Mean age was higher in the amiodarone group (69.2 vs. 67.6 years). After weighting, amiodarone initiation was associated with a higher risk of severe hypoglycemia compared with initiation of comparator antiarrhythmics (weighted HR 1.92; 95% CI, 1.12-3.30). The increased risk persisted across multiple sensitivity and subgroup analyses.

Initiation of amiodarone in patients receiving sulfonylureas was associated with a higher risk of hypoglycemia compared with other antiarrhythmics. Given the continued use of sulfonylureas in diabetes care, this finding highlights the need for caution and close monitoring during their concomitant use with amiodarone.