Concomitant Use of Sulfonylureas and β-Blockers and the Risk of Severe Hypoglycemia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study

OBJECTIVE The hypoglycemic potential of beta-blockers among users of sulfonylureas, drugs that strongly increase the risk of this potentially fatal adverse effect, is not well understood. Our population-based cohort study assessed the potential association between concomitant use of sulfonylureas and beta-blockers versus use of sulfonylureas alone and the risk of severe hypoglycemia. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink Aurum, we included patients initiating sulfonylureas between 1998 and 2020, excluding those with beta-blocker use in the past 6 months. Time-dependent Cox models estimated hazard ratios (HRs) with 95% CIs of severe hypoglycemia (hospitalization with or death resulting from hypoglycemia; ICD-10 codes E16.0, E16.1, and E16.2) associated with current concomitant use of sulfonylureas and beta-blockers compared with current sulfonylurea use alone, adjusted for baseline confounders. We also compared current concomitant use of sulfonylureas and non-cardioselective versus cardioselective beta-blockers. RESULTS Our cohort included 252,869 initiators of sulfonylureas (mean age 61.3 years; 43% female). Median follow-up was 7.9 years. The crude incidence rate of severe hypoglycemia was 7.8 per 1,000 per year. Concomitant use of sulfonylureas and beta-blockers was associated with an increased risk of severe hypoglycemia compared with sulfonylurea use alone (HR 1.53; 95% CI 1.42-1.65). There was no difference in the risk between concomitant use of sulfonylureas and noncardioselective beta-blockers and concomitant use of sulfonylureas and cardioselective beta-blockers (HR 0.95; 95% CI 0.74-1.24). CONCLUSIONS beta-blockers could further increase the risk of severe hypoglycemia when used concurrently with sulfonylureas. beta-blocker cardioselectivity did not seem to play a major role in this regard.