Abstract

Objective: Several studies have suggested an association between specific diabetes treatment and cancer mortality. We studied the association between metformin use and cancer mortality in a prospectively followed cohort.

Research design and methods: In 1998 and 1999, 1353 patients with type 2 diabetes mellitus were enrolled in the ZODIAC-study in the Netherlands. Vital status was assessed in January 2009. Cancer mortality rate was evaluated using standardized mortality ratios (SMR), and the association between metformin use and cancer mortality was evaluated with a Cox proportional hazard model, taking possible confounders into account.

Results: Median follow-up time was 9.6 years, average age at baseline was 68 years, and average HbA1c was 7.5%. Five hundred seventy patients died, of which 122 from malignancies. SMR for cancer mortality was 1.47 (95%CI 1.22-1.76). In patients taking metformin compared to patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95%CI 0.23-0.80), and the HR with every increase of 1 gram of metformin was 0.58 (95%CI 0.36-0.93).

Conclusions: In general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality when compared to non-metformin use. Although the design cannot be conclusive about causality, our results suggest a protective effect of metformin on cancer mortality.