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Metformin Use Is Associated with Improved Survival in Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy

Metformin is commonly prescribed for patients with type 2 diabetes mellitus (DM). We hypothesize that metformin plus androgen deprivation therapy (ADT) may be beneficial in combination. The objective was to assess this combination in a retrospective cohort of patients with advanced PCa.

Using national Veterans Affairs databases, we identified all men diagnosed with PCa between 2000-2008 that were treated with ADT with follow-up through May of 2016. Exclusions included treatment with ADT for ≤6 months or ADT receipt concurrently with localized radiation. Three patient cohorts were developed: No DM, DM no metformin, and DM on metformin. Cox proportional hazards ratios were calculated for overall survival (OS), skeletal-related events (SRE) and cancer-specific survival (CSS).

The cohort after exclusions consisted of 87,344 patients: 61% were no DM, 22% were DM no metformin, and 17% were DM on metformin. Cox proportional hazards analysis for OS showed improved survival in DM on metformin (HR 0.82, 95% CI 0.78-0.86) vs. DM no metformin (HR 1.03, 95% CI 0.99-1.08) with no DM as the referent group. Cox proportional hazards analysis for predictors of SRE revealed HR 0.82 (95% CI 0.72-0.93) for DM on metformin. Cox proportional hazards analysis for CSS showed improved survival in DM on metformin (HR 0.70, 95% CI 0.64-0.77) vs. DM no metformin (HR 0.93, 95% CI 0.85- 1.00) with no DM as the referent group.

Metformin use in Veterans with PCa receiving ADT is associated with improved oncologic outcomes. This association should be evaluated in a prospective clinical trial.

Authors: Kyle A. Richards, MD, Jinn-ing Liou, MS, Vincent L. Cryns, MD, Tracy M. Downs, MD, E. Jason Abel, MD, David F. Jarrard, MD
Author Affiliation: William S. Middleton Memorial Veterans Hospital, Department of Surgery, Section of Urology, The University of Wisconsin-Madison, Department of Urology, Madison, WI. 

https:/doi.org/10.1016/j.juro.2018.06.031
Metformin Use Is Associated with Improved Survival in Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy. Richards, Kyle A. et al. The Journal of Urology, ePub ahead of print, June 22, 2018.