Metformin and prostate cancer mortality: a meta-analysis
- 751 Downloads
Observational studies report conflicting results on the association between metformin exposure and prostate cancer outcomes. This meta-analysis summarizes studies reporting overall survival, prostate cancer-specific mortality, and biochemical recurrence.
PubMed and Embase were systematically reviewed to identify studies investigating the association between metformin use and clinical endpoints among men with prostate cancer while taking confounding by diabetes diagnosis into account. Pooled risk estimates (hazard ratios, HRs) and 95 % confidence intervals (CIs) were calculated using random-effects models. Sensitivity analyses for quality components and factors for heterogeneity were conducted.
Of 549 articles identified, nine retrospective cohort studies representing 9,186 patients were included. There was significant heterogeneity between studies, and studies differed in quality. Metformin use was associated with improved overall survival in studies with clear risk window definition (HR 0.88, 95 % CI 0.86–0.90, p < 0.001) and in studies with potential immortal time bias (HR 0.52, 95 % CI 0.41–0.65, p < 0.001). No significant association with prostate cancer-specific mortality was detected (HR 0.76, 95 % CI 0.44–1.31, p = 0.33). Metformin use was associated with a decreased risk of biochemical recurrence (HR 0.79, 95 % CI 0.63–1.00, p = 0.047).
This meta-analysis suggests a benefit of metformin in men with diabetes and prostate cancer. However, further carefully designed studies are needed to confirm findings and to assess potential generalization to non-diabetic, non-white, and less aggressively treated men with prostate cancer.
KeywordsProstate cancer Diabetes mellitus Metformin Mortality Biochemical recurrence Meta-analysis
Prostate cancer-specific mortality
- 95 % CI
95 % Confidence interval
Randomized controlled trial
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest to disclose.
- 5.Nathan DM, Buse JB, Davidson MB et al (2006) Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 29:1963–1972CrossRefPubMedGoogle Scholar
- 13.Saenz A, Fernandez-Esteban I, Mataix A, Ausejo M, Roque M, Moher D (2005) Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database Syst Rev 20(3):CD002966Google Scholar
- 21.Xu H, Aldrich MC, Chen Q et al (2015) Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality. J Am Med Inform Assoc 22(1):179–191Google Scholar
- 41.Spratt DE, Zhang Z, Zelefsky MJ (2013) Reply to Leah Bensimon, Samy Suissa, and Laurent Azoulay’s letter to the editor re: Daniel E. Spratt, Chi Zhang, Zachary S. Zumsteg, Xin Pei, Zhigang Zhang, Michael J. Zelefsky. metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality. Eur Urol 2013;63:709–16. Eur Urol 64:e29–e30CrossRefPubMedGoogle Scholar