Metformin, Asian ethnicity and risk of prostate cancer in type 2 diabetes: a systematic review and meta-analysis

Background: Metformin is associated with a reduced risk of some cancers but its effect on prostate cancer is unclear. Some studies suggest only Asians derive this benefit. Therefore, we undertook a systematic review with particular attention to ethnicity. Methods: Medline, Embase, Scopus, Web of Science, and EBM Reviews were searched from inception to 2015. Two reviewers identified and abstracted articles. Studies were pooled using random effects model and stratified by Westernvs Asian-based populations. Results: We identified 482 studies; 26 underwent full review. Of Western-based studies (n = 23), two were randomized trials and 21 were observational studies. All Asian-based studies (n = 3) were observational. There were 1,572,307 patients, 1,171,643 Western vs 400,664 Asian. Across all studies there was no association between metformin and prostate cancer (RR: 1.01, 95% CI: 0.86-1.18, I-2: 97%), with similar findings in Western-based trials (RR: 1.38, 95% CI: 0.72-2.64 I-2: 15%) and observational studies (RR: 1.03 95% CI: 0.94-1.13, I-2: 88%). Asian-based studies suggested a non-significant reduction (RR: 0. 75, 95% CI: 0.42-1.34, I-2: 90%), although these results were highly influenced by one study of almost 400,000 patients (propensity-adjusted RR: 0.47 95% CI 0.45-0.49). Removing this influential study yielded an estimate more congruent with Western-based studies (RR: 0.98 95% CI: 0.71-1.36, I-2: 0%). Conclusion: There is likely no association between metformin and risk of prostate cancer, in either Western-based or Asian-based populations after removing a highly influential Asian-based study.