(068) Risk of New-onset Type 2 Diabetes Mellitus Associated with 5-Alpha Reductase Inhibitors: A Nationwide Population-Based Study

Background: The 5-alpha reductase inhibitors (5-ARI) including finasteride and dutasteride are the most common medications for benign prostatic hyperplasia (BPH). Recently, the Saudi Food and Drug Authority (SFDA) recommended all health care professionals to be aware of the safety signal of diabetes mellitus (DM) associated with the use of finasteride. However, there are few studies on the potential adverse drug events regarding DM in patients with 5-ARI use in Korea.

Objectives: This study aimed to investigate the association between use of the 5-ARI and new-onset type2 DM among BPH patients.

Methods: We performed a population-based, retrospective cohort study using the Korean National Health Insurance claims data from 2012 to 2021. We selected patients aged 40 years and older who were newly diagnosed with BPH between 2014 and 2018 and excluded those with a history of DM or fasting blood sugar levels over 126 mg/dL. In consideration of the clinical setting, we analyzed the risk of type 2 DM in the combination users of 5-ARI and alpha-blockers (AB) compared with AB users. We used Cox proportional regression models after 1:1 propensity score (PS) matching to calculate the hazard ratio (HR) with 95% confidence interval (CI) of 5-ARI use on new-onset type 2 DM, adjusting for possible confounding risk factors. Subgroup analyses were conducted by specific medication ingredients, age, duration of use, body mass index (BMI) and fasting blood sugar levels.

Results: Among 529,072 eligible patients included in the study, 151,707 patients were treated with combination of 5-ARI and AB, and 377,365 patients were treated with AB. After 1:1 PS matching, each consisting of 151,707 patients, a total of 26,925 cases of type 2 DM were detected over a mean follow-up period of 5.1 years (14,267 among combination users of 5-ARI and AB; 12,658 among users of AB). The risk of new-onset type 2 DM was found to be statistically significantly higher in combination users of 5-ARI and AB compared to users of AB (adjusted HR: 1.13, 95% confidence interval (CI): 1.10-1.16). Subgroup analyses revealed variations in the risk of new-onset type 2 DM among combination users of 5-ARI and AB based on factors such as specific medication ingredients, age, duration of use, BMI and fasting blood sugar levels.

Conclusions: We confirmed a significant relationship between the use of 5-ARI and the risk of new-onset type 2 DM. We suggest regular monitoring for type 2 DM in clinical settings among individuals using 5-ARI, particularly those who are long-term users, while taking into account various patient conditions.