Cancer mortality reduction and metformin: a retrospective cohort study in type 2 diabetic patients

Aims: Few studies suggest that metformin decreases cancer mortality in type-2 diabetic patients (T2DP). We explored the association between the type and duration of antidiabetic therapies and cancer and other-than-cancer mortality in a T2DP cohort, taking into account the competing risks between different causes of death and multiple potential confounding effects. The mortality rates were compared with the general population from the same area. Methods: In 1995, all T2DP (n = 3685) at our diabetes clinic in Turin (similar to 12% of all T2DP in the city), without cancer at baseline, were identified. Vital status was assessed after a mean 4.5-year follow-up. Results: Metformin users had greater adiposity, while insulin users had more co-morbidities. All-cause-and cancer-related deaths occurred in: 9.2 and 1.6% of metformin users, 13.1 and 3.0% of sulfonylureas users and 26.8 and 4.8% of insulin users, respectively. In a Cox regression model for competing risks, adjusted for propensity score, metformin users showed a lower cancer mortality risk [hazard ratio (HR) = 0.56; 95% confidence interval (CI) 0.34-0.94], while insulin was positively associated with other-than-cancer mortality (HR = 1.56; 95% CI 1.22-1.99). Each 5-year metformin exposure was associated with a reduction in cancer death by 0.73, whereas every 5-year insulin exposure was associated with 1.25-fold increase in other-than-cancer death. Standardized mortality ratios for cancer and other-than-cancer mortality in metformin users were 43.6 (95% CI 25.8-69.0) and 99.1 (95% CI 79.3-122.5), respectively, in comparison with the general population. Conclusions: Metformin users showed a lower risk of cancer-related mortality than not users or patients on diet only; this may represent another reason to choose metformin as a first-line therapy in T2DP.