Oral glucose-lowering drugs and long-term risk of benign prostatic hyperplasia

Background. One of the most prominent threats for masculine health is comorbidity between benign prostatic hyperplasia (BPH) and diabetes mellitus type 2. Many publications suppose influence of hyperglycemia on lower urinary tract obstruction. Question about influence of the most common oral glucose-lowering drugs – biguanides (metformin hydrochloride) and third-generation sulfonylurea (glimepiride) has not been answered yet.

Aim. To assess whether glucose-lowering drugs affect risk of benign prostatic hyperplasia (BPH) in men with type 2 diabetes who initiated first-line treatment with either metformin or sulfonylurea monotherapy from 2012 until 2022 in the National Medical Research Center for Endocrinology.

Materials and methods. Single centre, retrospective, comparative study. Retrospective analysis of in-/outpatient medical cards. Primary outcome measures: Rates of subsequent BPH, identified based on community prescriptions for BPH-related treatment or hospital BPH diagnoses, and rates of transurethral resection of the prostate (TURP). Rates in metformin hydrochloride and sulfonylurea users were compared overall and stratified by 6-month haemoglobin A1c (HbA_1c) using Cox regression.

Results. In 95 metformin initiators with a median follow-up of 10 years, the 10-year cumulative BPH incidence was 25.7% (25 cases; 95% CI 24.2–27.1). Compared with 95 sulfonylurea users [median follow-up 8 years, 10-year cumulative incidence 27.4% (17 cases; 95% CI 16.2–18.6)], the crude HR for BPH was 0.83 (95% CI 0.77–0.89) and adjusted HR in the ITT analyses was 0.97 (95% CI 0.88–1.06). For TURP, the adjusted HR was 0.96 (95% CI 0.63–1.46). In the as-treated analysis, adjusted HR for BPH was 0.91 (95% CI 0.81–1.02).

Conclusion. Compared with sulfonylurea, metformin did not substantially reduce the incidence of BPH in men with diabetes.