Metformin Active Surveillance Trial in Low-Risk Prostate Cancer.

Metformin, a commonly prescribed antidiabetic agent, has demonstrated antitumor activity in preclinical studies and observational data, prompting investigation into its potential to delay PCa progression.

二甲双胍是一种常用的抗糖尿病药物，在临床前研究和观察性数据中显示出抗肿瘤活性，这促使人们研究其延缓前列腺癌进展的潜力。

patients_and_methods

The Metformin Active Surveillance Trial (MAST) was a multicenter, randomized, double-blind, placebo-controlledphase III trial evaluating the efficacy of metformin in men with low-risk, localized PCa managed with AS.

Metformin活性监测试验（MAST）是一项多中心、随机、双盲、安慰剂对照的III期临床试验，评估了在低危、局限性前列腺癌（PCa）患者中，使用二甲双胍进行主动监测（AS）的疗效。

Eligible participants were randomly assigned 1:1 to receive either metformin (850 mg twice daily) or placebo and were followed for up to 36 months.

符合条件的参与者按1:1的比例随机分配接受二甲双胍（每日两次，每次850毫克）或安慰剂治疗，并被随访最多36个月。

The primary end point was time to progression, defined as therapeutic and/or pathologic progression.

主要终点是进展时间，定义为治疗和/或病理进展。

Progression-free survival(PFS) was assessed using Kaplan-Meier analysis and Cox proportional hazards models.

使用Kaplan-Meier分析和Cox比例风险模型评估无进展生存期（PFS）。

Results

A total of 408 patients were randomly assigned (205 metformin, 203 placebo).

共有408名患者被随机分配（205名接受二甲双胍治疗，203名接受安慰剂治疗）。

After a median follow-up of 36 months, 144 participants experienced progression (70 metformin, 74 placebo), with no significant difference in PFS (hazard ratio[HR], 1.09 [95% CI, 0.79 to 1.52]; P = .59).

经过中位随访36个月后，共有144名参与者出现疾病进展（二甲双胍组70人，安慰剂组74人），无显著差异的无进展生存期（风险比[HR]，1.09 [95% 置信区间，0.79至1.52]；P = .59）。

Negative biopsy rates at 36 months were 41.0% (metformin) versus 31.1% (placebo; P = .181).

36个月时，二甲双胍组的阴性活检率为41.0%，而安慰剂组为31.1%（P = .181）。

In prespecified subgroup analysis, metformin was associated with increased pathologic progression among obese patients (BMI ≥ 30; HR, 2.36 [95% CI, 1.21 to 4.59]; P = .0092).

在预先指定的亚组分析中，二甲双胍与肥胖患者（BMI ≥ 30）的病理进展增加有关（HR, 2.36 [95% 置信区间, 1.21 至 4.59]; P = .0092）。

Conclusions

Metformin did not reduce progression in men with low-risk PCa on AS.

在低危前列腺癌患者中，二甲双胍并未减少其进展。

The observed adverse effect in obese patients merits further investigation.

在肥胖患者中观察到的不良反应值得进一步研究。