The relationship between metformin and prostate cancer has not been well studied, but the results have been inconsistent. Mark A. Preston, MD, of Massachusetts General Hospital, and others found that metformin reduced prostate cancer risk in a large nested case-control study, the results of which are published in this issue of European Urology. The researchers analyzed data from the Danish Tumor Registry and included 12,226 Danish prostate cancer patients between 1989 and 2011, and used hazard set sampling to select 10 population-based controls for each case (122,260 total controls), with controls selected based on being born in the same year as the case and alive at the study index date. Also, the researchers used data from the Arahus University prescription database to analyze the population using antidiabetic drugs and divided them into the following groups: taking metformin but not using insulin, taking metformin and insulin, taking metformin, using other oral antidiabetic drugs, and not using drugs. The results found that the risk of Pca diagnosis was 16% lower in patients taking metformin than in those who never used it. In contrast, there was no reduction in the risk of PCa in patients with diabetes who did not use medication or in patients who used other oral hypoglycemic agents, except for a reduction in risk in patients who used insulin. In the PSA group, the risk of PCa was lower with metformin compared with no metformin. The duration, dose and cumulative dose of metformin were negatively associated with the risk of prostate cancer. The risk was not reduced in patients using other oral hypoglycemic agents and insulin. Metformin reduces the risk of prostate cancer, possibly by reducing insulin-related tumorigenic effects, or by acting directly on cancer cells. The authors also suggested that diabetes itself may reduce prostate cancer risk, which may be a concomitant effect; it may also be due to the reduced diagnostic intensity in diabetic patients without prostate cancer symptoms. However, randomized controlled clinical trials of metformin for prostate cancer prevention remain promising because clinical and preclinical studies suggest that patients may benefit from it.