Risk of Hospital Presentation with Hypoglycemia Among Users of Beta-blockers with Diabetes: Population-Based Nested Case-Control Study.

Abstract

Background: Beta-adrenergic antagonists ("beta-blockers") have metabolic effects that influence risk of hypoglycemia in persons with diabetes. This risk may be elevated upon initial exposure and may vary among agents in the class.

Objective: To explore differences in the risk of hypoglycemia among new and prevalent users of individual beta-blockers in people with diabetes.

Design: Population-based nested case-control study. Cases of hypoglycemia, defined using emergency department or hospital admitting diagnosis, were matched with up to ten controls on age, sex, diabetes duration, and at least one prescription record for a beta-blocker in the 365 days preceding the hypoglycemic event or the equivalent date for controls (index date). Beta-blocker exposure was categorized as new, prevalent, recent, and remote use based on a pre-index 90-day (primary) and 30-day (secondary) exposure ascertainment period.

Participants: Persons aged 66 years or older with diabetes in Ontario, Canada.

Main measures: Conditional logistic regression models were used to calculate adjusted odds ratios with 95% confidence intervals for the association between initiation of a beta-blocker and the risk of hypoglycemia.

Key results: We identified 26,545 cases and 265,450 matched controls. The median age of patients was 78 years, 50% were female, and their median time since diabetes diagnosis of 11 years. Compared with prevalent use of beta-blockers, new use was associated with an increased odds of hypoglycemia (adjusted odds ratio [aOR] 1.87, 95% confidence interval [CI] 1.75-1.99). In contrast, neither recent use (aOR 1.03, 95% CI 0.98-1.08) nor remote use (aOR 0.82, 95% CI 0.77-0.87) was associated with an increased odds of hypoglycemia. Among individual agents, nonselective beta-blockers had the highest risk of hypoglycemia associated with new use.

Conclusions: In older patients with diabetes, the initiation of beta-blockers is associated with a near-doubling of the odds of a hospital encounter for hypoglycemia.