The preventive effect of metformin on progression of benign prostate hyperplasia: A nationwide population-based cohort study in Korea

Metformin, a first-line treatment for type 2 diabetes mellitus (T2DM), has recently been recognized for its pleotropic anti-proliferative, anti-cancer, and anti-aging effects. Contrary to the studies characterizing metformin effects in prostate cancer, little is known about these effects in BPH progression. With the Sample Cohort DB data during 2007 and 2017 from the Health Insurance Review and Assessment Service (HIRA) in South Korea, we investigated the preventative effect of metformin on BPH progression. The study population consisted of 211,648 BPH naïve patients that were diagnosed with BPH in 2009 and a follow-up occurrence of prostatectomy until 2017 that was defined as progression of BPH. These patients were divided into three treatment groups: without T2DM, T2DM without metformin, and T2DM with metformin. The hazard ratio in the T2DM with metformin group was 0.86 for prostatectomy compared to the group without T2DM (CI = 0.77–0.96, P value = 0.007) after adjusting for confounding factors such as age, comorbidity, residential area, level of hospital, and category of BPH medications. The T2DM with high-dose metformin group had a significantly lower risk of prostatectomy with hazard ratio of 0.76 (CI = 0.62–0.92, P value = 0.005) in stratified analysis. Our results suggest that metformin may improve BPH progression based on the reduced risk of prostatectomy, although T2DM effects on BPH were unclear. Future observational studies and prospective trials are needed to confirm the effects of metformin on BPH progression.

二甲双胍（Metformin）作为2型糖尿病（type 2 diabetes mellitus, T2DM）的一线治疗药物，近年来被证实具有多效性的抗增殖、抗肿瘤及抗衰老活性。相较于针对二甲双胍在前列腺癌中作用的相关研究，目前学界对其在良性前列腺增生（Benign Prostatic Hyperplasia, BPH）进展中的调控作用尚所知甚少。本研究依托韩国健康保险审查与评估服务（Health Insurance Review and Assessment Service, HIRA）2007至2017年的样本队列数据库（Sample Cohort DB）数据，探讨了二甲双胍对BPH进展的预防效果。研究队列共纳入211648例初诊BPH患者，这些患者于2009年确诊BPH，且随访至2017年期间发生前列腺切除术（prostatectomy）者被定义为BPH进展。研究将所有患者分为三组：无T2DM组、未使用二甲双胍的T2DM组及使用二甲双胍的T2DM组。经年龄、合并症（comorbidity）、居住区域、医院等级及BPH治疗药物类别等混杂因素校正后，与无T2DM组相比，使用二甲双胍的T2DM组患者接受前列腺切除术的风险比（hazard ratio）为0.86（置信区间CI=0.77–0.96，P值=0.007）。分层分析显示，高剂量二甲双胍的T2DM组患者前列腺切除术风险显著降低，风险比为0.76（CI=0.62–0.92，P值=0.005）。本研究结果表明，尽管T2DM对BPH的影响尚不明确，但基于前列腺切除术风险的降低，二甲双胍或可改善BPH进展。未来仍需开展观察性研究及前瞻性试验，以证实二甲双胍对BPH进展的作用。