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

Diabetes Care. 2023 Feb 1;46(2):377-383. doi: 10.2337/dc22-1584.

Abstract

Objective: The hypoglycemic potential of β-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 β-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 β-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 β-blockers compared with current sulfonylurea use alone, adjusted for baseline confounders. We also compared current concomitant use of sulfonylureas and non-cardioselective versus cardioselective β-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 β-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 β-blockers and concomitant use of sulfonylureas and cardioselective β-blockers (HR 0.95; 95% CI 0.74-1.24).

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Female
  • Humans
  • Hypoglycemia* / chemically induced
  • Hypoglycemia* / epidemiology
  • Hypoglycemic Agents / adverse effects
  • Male
  • Middle Aged
  • Sulfonylurea Compounds / adverse effects

Substances

  • Sulfonylurea Compounds
  • Hypoglycemic Agents
  • Adrenergic beta-Antagonists

Grants and funding