Risk of Incident Cancer in Veterans with Diabetes Who Use Metformin Versus Sulfonylureas

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans. This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfonylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.