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.