Risk of incident diabetes after initiation of 5α-reductase inhibitor plus α-blocker combination therapy: A nationwide cohort study with age-specific analyses.

AIMS: To evaluate the association between initiation of 5α-reductase inhibitor plus α-blocker combination therapy (5ARI + AB) and incident diabetes compared with α-blocker (AB) monotherapy in men with benign prostatic hyperplasia. METHODS: We conducted a nationwide active-comparator, new-user cohort study using the Korean National Health Insurance Service database. Men aged ≥ 40 years initiating 5ARI + AB or AB monotherapy during 2014-2018 were matched 1:1 by propensity score. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using stratified Cox models. RESULTS: Among 151,707 matched pairs, 5ARI + AB initiation was associated with a higher risk of incident diabetes than AB monotherapy (18.4 vs 16.3 per 1,000 person-years; adjusted HR 1.13, 95% CI 1.10-1.16). The association differed by age, with increased risk among men aged < 65 years (adjusted HR 1.33, 95% CI 1.27-1.39), whereas estimates among men aged ≥ 65 years were sensitive to competing-risk handling and were close to the null after accounting for competing mortality. The association persisted after a 12-month lag but attenuated in the as-treated analysis. CONCLUSIONS: 5ARI + AB initiation was associated with a modestly higher risk of incident diabetes, particularly among men aged < 65 years. Age-related heterogeneity and sensitivity to exposure assumptions warrant consideration when evaluating metabolic safety.