Abstract
Background: Beta-blockers may interact with sulfonylureas (SU) and increase their hypoglycemic risk. Our study assessed the potential association between concomitant use of SU and beta-blockers and the risk of severe hypoglycemia. Methods: We used the UK's Clinical Practice Research Datalink linked to hospitalization and vital statistics data of patients with type 2 diabetes initiating SU 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 associated with current concomitant use of SU and beta-blockers compared to current SU use alone, adjusted for baseline confounders. To address potential residual confounding, we repeated the analysis with current concomitant use of SU and thiazide diuretics as reference group. We also compared current concomitant use of SU and non-cardioselective (propranolol, carvedilol, sotalol, labetalol) vs. cardioselective beta-blockers (acebutolol, atenolol, bisoprolol, metoprolol, nebivolol, esmolol) to explore the role of beta-blocker cardioselectivity in this association. Results: Our cohort included 252,869 SU initiators. The crude incidence rate of severe hypoglycemia was 7.8 per 1000/year. Concomitant use of SU and beta-blockers was associated with an increased risk of severe hypoglycemia compared to SU use alone (HR, 1.53; 95% CI, 1.42-1.65) . Changing the reference group led to consistent findings (HR, 1.69; 95% CI, 1.42-2.01) . There was no difference in the risk when comparing concomitant use of SU and non-cardioselective beta-blockers to concomitant use of SU and cardioselective beta-blockers (HR, 0.95; 95% CI, 0.74-1.24) . Conclusion: Our large cohort study showed an increased risk of severe hypoglycemia associated with concomitant use of SU and beta-blockers compared to SU use alone. This association did not vary with beta-blocker cardioselectivity. Disclosure J.Dimakos: None. Y.Cui: None. R.W.Platt: Consultant; Amgen Inc., Biogen, Merck & Co., Inc., Nant Pharma, Pfizer Inc. C.Renoux: None. K.B.Filion: None. A.Douros: None. Funding Canadian Institutes of Health Research (PJT-165882)
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