In this systematic review, metformin was associated with the best outcomes.
The combination of diabetes and heart failure imposes a greater mortality burden than either condition alone. Nonetheless, we know very little about the association between antidiabetic drugs and outcomes in patients with both conditions. In a systematic review, Canadian investigators identified eight studies (only 1 was a randomized trial) that assessed the risk for mortality or hospital admission in heart failure patients taking antidiabetic agents. Four studies evaluated the effect of insulin (9104 patients); three examined metformin (3327 patients); four evaluated thiazolidinediones (3409 patients); and two studies compared sulfonylureas with other agents (8918 patients).
In three of four studies, insulin was associated with an increased risk for death (odds ratio, 1.25). In two studies, metformin was associated with reduced all-cause mortality (hazard ratio, 0.86 compared with other antidiabetic drugs and insulin; HR, 0.70 compared with sulfonylureas); a third study showed a similar trend. Metformin was not associated with an increased risk for hospitalization. In four studies, use of thiazolidinediones was associated with reduced mortality (OR, 0.83) but an increased risk for hospitalization (OR, 1.13). The two studies of sulfonylureas had conflicting results.
Comment: At first glance, this study suggests that metformin is the only antidiabetic drug not associated with any measurable harm in patients with heart failure and that insulin might increase risk for death. However, this analysis mainly drew from observational studies: Insulin use might have been a marker for more-severe underlying disease (rather than a cause of death), and metformin use might have been a marker for less-severe underlying disease. This systematic review should generate a more comprehensive randomized controlled trial to more fully describe outcomes of antidiabetic treatment in patients with diabetes and heart failure.
Published in Journal Watch General Medicine October 9, 2007
Eurich DT et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: Systematic review. BMJ 2007 Sep 8; 335:497.