Metformin does not prevent progression of low-risk prostate cancer

Patients with low-risk, localised prostate cancer who are suitable for active surveillance do not benefit from daily use of metformin. The results of the phase 3 MAST study suggest that metformin is potentially detrimental in patients with high BMI.

Previously, it was suggested that metformin could be a useful adjuvant agent in cancer management, with biological, epidemiological, and clinical data offering a rationale for its use in prostate cancer [1]. However, much of the literature consists of retrospective analyses, where metformin use is associated with type 2 diabetes.

The phase 3 MAST trial (NCT01864096) is the first prospective randomised study to explore the effect of daily metformin use on the progression of low-risk, localised prostate cancer. Dr Anthony Joshua (Princess Margaret Cancer Centre, Canada) presented the results [2].

In the study, 407 men with newly diagnosed low-risk, localised prostate cancer were 1:1 randomised to active surveillance plus metformin or active surveillance plus placebo. Patients diagnosed with type 1 or type 2 diabetes were excluded. The primary endpoints were time to pathological progression and time to definitive therapy. Biopsies were performed at baseline and at 18 and 36 months of follow-up.

Metformin did not delay pathological progression compared with placebo (HR 1.08; 95% CI 0.78–1.50; P=0.64) but did increase therapeutic progression (HR 1.75; 95% CI 0.99–3.03; P=0.05). Exploratory subgroup analysis showed significantly increased pathological progression in participants with BMI ≥30 at study entry (n=105) treated with metformin versus placebo (HR 2.39; 95% CI 1.20–4.75; P=0.01).

Dr Joshua concluded that “metformin does not prevent the progression of low-risk, localised prostate cancer suitable for active surveillance. In patients with high BMI, metformin may even be detrimental. Therefore, further research is needed to understand the effects of metformin on prostate cancer outcomes.”

1. Coyle C, et al. Ann Oncol. 2016;27:2184-2195.
2. Fleshner NE, et al. A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: the MAST (Metformin Active Surveillance Trial) study. Abstract LBA5002, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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Posted on 18 July 202418 July 2024