Concomitant use of sulfonylureas and beta-blockers and the risk of severe hypoglycemia among patients with type 2 diabetes: a population-based cohort study

Background: 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.

Methods: Using the UK's 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% confidence intervals (CIs) of severe hypoglycemia (hospitalization with or death due to hypoglycemia; ICD-10 codes: E16.0, E16.1, E16.2) associated with current concomitant use of sulfonylureas and beta-blockers compared to 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 252,866 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 1000/year. Concomitant use of sulfonylureas and beta-blockers was associated with an increased risk of severe hypoglycemia compared to 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 non-cardioselective beta-blockers and concomitant use of sulfonylureas and cardioselective beta-blockers (HR, 0.95; 95% CI, 0.74-1.24).

Conclusion: Beta-blockers could further increase the risk of severe hypoglycemia when used concurrently with sulfonylureas. Beta-blocker cardioselectivity did not appear to play a major role in this regard.