Login to Access Video or Poster Abstract: MP53-08
Sources of Funding: Department of Defense

Introduction

Metformin is a commonly prescribed glucose-lowering therapy for patients with type 2 diabetes mellitus (T2DM). Basic research supports a synergistic anti-neoplastic effect of metformin for various cancers including prostate cancer (PC). We hypothesize that metformin plus androgen deprivation therapy (ADT) may be synergistic in men with advanced PC.

Methods

Using national Veterans Affairs databases, we identified all men diagnosed with PC between 2000-2008 that were treated with ADT and had follow-up through October of 2015. We excluded patients that were treated with ADT for ≤6 months or were receiving ADT concurrently with localized radiation therapy. Three cohorts were identified including non-diabetics, diabetics on metformin, and diabetics not on metformin. Our primary outcome was overall survival (OS) and secondary outcomes included skeletal related events (SRE) and PC-specific survival.

Results

The total cohort after exclusions consisted of 87,344 patients of which 53,893 (61%) were non-diabetics, 14,517 (17%) were diabetics on metformin and 18,934 (22%) were diabetics not on metformin. Mean age was 75 ±11y (non-diabetics), 71 ±12 (diabetics on metformin), and 75 ±10 (diabetics not on metformin), p<0.001. The median OS was 7.1, 9.1 and 7.4 y respectively (p<0.001). Multivariable Cox proportional hazards analysis assessing for predictors of OS showed improved survival in diabetics on metformin (HR 0.77, 95% CI 0.74-0.81; p<0.001) vs. diabetics not on metformin (HR 0.99, 95% CI 0.95-1.03; p=0.5) with non-diabetics as referent group while controlling for age, co-morbidity, and Gleason score. Assessing for predictors of SRE revealed no association between metformin use (HR 0.99, 95% CI 0.92-1.07; p=0.8) and SRE. Lastly, PC-specific survival was improved in diabetics on metformin (HR 0.72, 95% CI 0.67-0.78; p<0.001) and to a lesser extent diabetics not on metformin (HR 0.87, 95% CI 0.81- 0.93; p<0.001) with non-diabetics as referent group.

Conclusions

Metformin use in Veterans with advanced PC receiving ADT is associated with improved OS and cancer-specific survival. Improved outcomes for PC patients receiving metformin should be evaluated in a prospective clinical trial.

Funding

Department of Defense