World J Mens Health.  2023 Jul;41(3):680-691. 10.5534/wjmh.220133.

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

  • 1Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
  • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • 3Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan


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.
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).
A significantly lower risk of LUTS/BPH is observed in males with type 2 diabetes who use metformin.


Benign prostatic hyperplasia; Lower urinary tract symptoms; Metformin; National Health Insurance; Pharmacoepidemiology; Taiwan
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