Metformin use and pancreatic cancer survival among non-Hispanic white and African American U.S. Veterans with diabetes mellitus

Background: The effect of metformin use on survival among patients with pancreatic ductal adenocarcinoma (PDAC) is controversial. Furthermore, there are no data on African American patients. To address these, we analyzed data from the United States Veterans Health Administration (VHA). Methods: A population-based retrospective cohort study evaluating overall survival among 3,811 patients with PDAC with preexisting diabetes mellitus, diagnosed with PDAC within the VHA between 1998 and 2013. We calculated HRs and 95% confidence intervals (CI) using multivariable adjusted time-varying Cox proportional hazards regression to control for immortal time bias and confounders. Results: Metformin use was not associated with overall survival in the complete analyses (HR ¼ 1.05; 95% CI, 0.92–1.14; P ¼ 0.28). However, among patients who were metformin naïve at the time of PDAC diagnosis (N ¼ 1,158), metformin use was associated with improved overall survival in non-Hispanic white patients (HR ¼ 0.78; 95% CI, 0.61–0.99; P ¼ 0.04), but not African American patients (HR ¼ 1.20; 95% CI, 0.75–1.93; P ¼ 0.45). The survival benefit among non-Hispanic whites was limited to patients with metastatic disease (HR ¼ 0.67; 95% CI, 0.44–1.01; P ¼ 0.06). Among African American patients with metastatic disease, HR was 1.30 (95% CI, 0.77–2.53; P ¼ 0.28). There was a suggestion of heterogeneity by race in patients with metastatic disease (P_{heterogeneity} ¼ 0.05). Conclusions: We observed no associations between metformin use and survival in patients with PDAC, but there appears to be a survival benefit among non-Hispanic white patients who were metformin naïve at the time of PDAC diagnosis. Impact: If confirmed in other studies, our findings suggest that metformin as an adjunctive treatment for PDAC may not improve survival among African American patients.