Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study

Aims/hypothesis The safety of metformin in heart failure has been questioned because of a perceived risk of life-threatening lactic acidosis, though recent studies have not supported this concern. We investigated the risk of all-cause mortality associated with individual glucose-lowering treatment regimens used in current clinical practice in Denmark. Methods All patients aged >= 30 years hospitalised for the first time for heart failure in 1997-2006 were identified and followed until the end of 2006. Patients who received treatment with metformin, a sulfonylurea and/or insulin were included and assigned to mono-, bi- or triple therapy groups. Multivariable Cox proportional hazard regression models were used to assess the risk of all-cause mortality. Results A total of 10,920 patients were included. The median observational time was 844 days (interquartile range 365-1,395 days). In total, 6,187 (57%) patients died. With sulfonylurea monotherapy used as the reference, adjusted hazard ratios for all-cause mortality associated with the different treatment groups were as follows: metformin 0.85 (95% CI 0.75-0.98, p=0.02), metformin+sulfonylurea 0.89 (95% CI 0.82-0.96, p=0.003), metformin+insulin 0.96 (95% CI 0.82-1.13, p=0.6), metformin+insulin+sulfonylurea 0.94 (95% CI 0.77-1.15, p=0.5), sulfonylurea+insulin 0.97 (95% CI 0.86-1.08, p=0.5) and insulin 1.14 (95% CI 1.06-1.20, p=0.0001). Conclusions/interpretation Treatment with metformin is associated with a low risk of mortality in diabetic patients with heart failure compared with treatment with a sulfonylurea or insulin.