Effect of Metformin on Lower Urinary Tract Symptoms in Male Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study in Taiwan

Purpose: This study investigated the risk of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) associated with metformin use. Materials and Methods: We used the database of Taiwan's National Health Insurance to create 9,833 pairs of ever users and never users of metformin matched on propensity score. They were males with a new diagnosis of type 2 diabetes during 1999-2005. The incidence of LUTS/BPH was calculated from January 1, 2006 until December 31, 2011. We estimated hazard ratios by Cox regression weighted on propensity score. Results: There were 515 incident cases in ever users after a median follow-up of 5.4 years (incidence rate: 11.24 per 1,000 person-years) and 682 cases in never users after 5.2 years (15.92 per 1,000 person-years). The hazard ratio (HR) that compared ever to never users was 0.69 (95% confidence interval [CI], 0.62-0.78). The HRs that compared ever users categorized into quartiles of cumulative duration (<19.33, 19.33-41.56, 41.57-67.17, and >67.17 mo) to never users were 1.02 (0.84-1.23), 1.01 (0.86-1.20), 0.57 (0.47-0.69), and 0.40 (0.32-0.49), respectively. For the quartiles of cumulative dose of <582.00, 582.00-1,361.00, 1,361.01-2,449.00, and >2,449.00 g, the respective HRs were 1.03 (0.85-1.24), 0.96 (0.81-1.13), 0.60 (0.49-0.72), and 0.40 (0.32-0.50). The lower risk was significant in all quartiles of defined daily dose. However, a larger daily dose was associated with a greater risk reduction. There were no significant interactions between metformin and other antidiabetic drugs. Patients who used rosiglitazone and/or pioglitazone without metformin had a significantly higher risk (HR, 1.33; 95% CI, 1.09-1.63) and a combination with metformin attenuated such an adverse impact (HR, 0.78; 95% CI, 0.66-0.91). Conclusions: A significantly lower risk of LUTS/BPH is observed in males with type 2 diabetes who use metformin.