Haring Antti, Murtola Teemu J, Talala Kirsi, Taari Kimmo, Tammela Teuvo L J, Auvinen Anssi
a School of Medicine , University of Tampere , Tampere , Finland.
b Department of Urology , Tampere University Hospital , Tampere , Finland.
Scand J Urol. 2017 Feb;51(1):5-12. doi: 10.1080/21681805.2016.1271353. Epub 2017 Jan 13.
Diabetic men have lowered overall prostate cancer (PCa) risk, while their risk of high-grade disease may be elevated. The antidiabetic drug metformin may reduce the risk. This study evaluated PCa incidence among users of metformin and other antidiabetic drugs in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).
The study population (78,615 men) was linked to the national prescription database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for PCa were estimated using Cox regression, with medication use as a time-dependent variable. The effect of diabetes was estimated by comparing antidiabetic drug users to non-users, while drug-specific effects were evaluated within antidiabetic drug users. Analyses were performed in both study arms of FinRSPC.
Compared to non-users, men using antidiabetic drugs had lowered overall PCa risk (HR 0.85, 95% CI 0.79-0.92), and this association was not affected by PCa screening. However, the risk of metastatic PCa was increased (HR 1.44, 95% CI 1.09-1.91). Among antidiabetic drug users, metformin decreased overall PCa risk (HR 0.81, 95% CI 0.69-0.95) in a dose-dependent manner. When stratified by FinRSPC study arm, the risk reduction was observed only in the screening arm. Sulphonylureas increased the risk of metastatic PCa (HR 2.04, 95% CI 1.11-3.77). Use of thiazoledenediones or insulin was not associated with PCa risk.
Among antidiabetic drug users, metformin lowered the overall PCa risk, while the risk of metastatic disease was elevated in sulphonylurea users. As sulphonylureas stimulate insulin secretion, the results suggest that hyperinsulinemia may be a risk factor for PCa.
糖尿病男性患前列腺癌（PCa）的总体风险较低，但其患高级别疾病的风险可能会升高。抗糖尿病药物二甲双胍可能会降低这种风险。本研究在芬兰前列腺癌筛查随机研究（FinRSPC）中评估了二甲双胍和其他抗糖尿病药物使用者的PCa发病率。
研究人群（78615名男性）与国家处方数据库相关联。使用Cox回归估计PCa的风险比（HRs）和95%置信区间（CIs），将药物使用作为时间依赖性变量。通过比较抗糖尿病药物使用者和非使用者来估计糖尿病的影响，同时在抗糖尿病药物使用者中评估药物特异性影响。在FinRSPC的两个研究组中都进行了分析。
与非使用者相比，使用抗糖尿病药物的男性患PCa的总体风险较低（HR 0.85，95% CI 0.79 - 0.92），并且这种关联不受PCa筛查的影响。然而，转移性PCa的风险增加（HR 1.44，95% CI 1.09 - 1.91）。在抗糖尿病药物使用者中，二甲双胍以剂量依赖性方式降低了总体PCa风险（HR 0.81，95% CI 0.69 - 0.95）。按FinRSPC研究组分层时，仅在筛查组中观察到风险降低。磺脲类药物增加了转移性PCa的风险（HR 2.04，95% CI 1.11 - 3.77）。噻唑烷二酮类药物或胰岛素的使用与PCa风险无关。
在抗糖尿病药物使用者中，二甲双胍降低了总体PCa风险，而磺脲类药物使用者中转移性疾病的风险升高。由于磺脲类药物刺激胰岛素分泌，结果表明高胰岛素血症可能是PCa的一个风险因素。
