(DCP043) FLUOROQUINOLONES AND THE RISK OF SEVERE HYPOGLYCEMIA AMONG SULFONYLUREA USERS: POPULATION-BASED COHORT STUDY

Background: Fluoroquinolones may cause hypoglycemia in rare occasions. The hypoglycemic risk of fluoroquinolones could become clinically relevant for patients with diabetes using sulfonylureas, who are already at a high baseline risk of developing this potentially fatal adverse effect. The clinical relevance is further underscored by the common concomitant use of antidiabetic drugs and antibiotics resulting from the elevated risk of bacterial infections among patients with diabetes. To address this knowledge gap, our population-based cohort study assessed whether concomitant use of sulfonylureas and fluoroquinolones is associated with an increased risk of severe hypoglycemia compared to concomitant use of sulfonylureas and amoxicillin among patients with type 2 diabetes.

METHODS AND RESULTS: We used a primary care database containing electronic medical records from patients in the United Kingdom (Clinical Practice Research Datalink Aurum) linked to hospitalization and vital statistics data. Out of a base cohort of patients initiating sulfonylureas between 1998 and 2020, we assembled a study cohort of patients co-exposed to sulfonylureas and either a fluoroquinolone or amoxicillin. Study cohort entry date was the date of antibiotic initiation while on a sulfonylurea. Using an intention-to-treat exposure definition, we assessed the 30-day risk of severe hypoglycemia (defined as hospitalization with or death due to hypoglycemia) associated with use of fluoroquinolones compared to use of amoxicillin. The two groups were matched on prior use of sulfonylureas and antibiotics, and on propensity score. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycemia in the matched cohort. Secondary analyses stratified by age, sex, and hemoglobin A1c. Sensitivity analyses addressed the impact of different potential sources of bias.

Out of 325,000 patients initiating sulfonylureas during the study period, 143,417 were later co-exposed to either a fluoroquinolone or amoxicillin. Concomitant use of sulfonylureas and fluoroquinolones was not associated with an increased risk of severe hypoglycemia (HR, 1.17; 95% CI, 0.91-1.50) compared to concomitant use of sulfonylureas and amoxicillin (Figure). There was no effect modification by sex or hemoglobin A1c. Fluoroquinolones were associated with an increased risk of severe hypoglycemia (HR, 2.90; 95% CI, 1.41-5.97) in patients < 65 years, but not in those ≥65 years (HR, 1.03; 95% CI, 0.79-1.35; Table). Sensitivity analyses were consistent with the primary analysis (HRs ranging from 0.92 to 1.19).

Conclusion: In a population with a high baseline risk of hypoglycemia, fluoroquinolones were not associated with an excess risk of this adverse effect. An excess risk among younger adults is possible.