Metformin Improves Survival in Patients with Pancreatic Ductal Adenocarcinoma and Pre-Existing Diabetes: A Propensity Score Analysis

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity. METHODS: We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011. The diabetic comorbidity severity index (DCSI) controlled for DM severity. Inverse propensity weighted Cox Proportional-Hazard Models assessed the association between metformin use and overall survival adjusting for relevant confounders. RESULTS: We identified 1,916 patients with PDAC and pre-existing DM on hypoglycemic medications at least 1 year before cancer diagnosis. Of these, 1,098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (P < 0.01). After adjusting for confounders including DCSI, Charlson score, and chronic kidney disease (CKD), patients on metformin had a 12% decreased risk of mortality compared with patients on other medications (hazard ratio (HR): 0.88, 95% confi dence interval (CI): 0.81-0.96, P < 0.01). In stratified analysis, differences persisted regardless of the Charlson score, the DCSI score, the presence of kidney disease, or the use of insulin/other hypoglycemic medications (P < 0.01 for all). CONCLUSIONS: Metformin is associated with increased survival among diabetics with PDAC. If confirmed in a prospective study, then these results suggest a possible role for metformin as an adjunct to chemotherapy among diabetics with PDAC.