Effect of glucose-lowering therapies on heart failure.

Heart failure is one of the most common comorbidities of diabetes mellitus. Glucose-lowering therapies that can prevent heart failure or improve outcomes in patients with established heart failure are of critical importance among those with type 2 diabetes. Several types of glucose-lowering drugs have been assessed in this setting. Metformin has been shown to modestly improve the outcomes of patients with heart failure, whereas the effect of insulin in those with established heart failure is less clear. The effect of sulfonylureas on improving heart failure is controversial; observational reports have suggested that they are harmful in these patients, but these data have not been confirmed in randomized, controlled trials. Thiazolidinediones are contraindicated in patients with established heart failure and have also been known to cause heart failure. Furthermore, certain dipeptidyl peptidase 4 inhibitors seem to increase heart failure hospitalization. The effects of glucagon-like peptide 1 receptor agonists might differ in patients with or without established heart failure, particularly those with decompensated heart failure with a reduced ejection fraction. However, perhaps the most important finding has been that sodium/glucose cotransporter 2 (SGLT2; also known as SLC5A2) inhibitors reduce heart failure hospitalizations and, in the case of empagliflozin, markedly reduce the rate of cardiovascular death. Given the known neutral (or even harmful) effects of other glucose-lowering drugs on heart failure outcomes, SGLT2 inhibitors might well be considered the drug class of choice in patients with diabetes and heart failure, or in those at high risk of developing heart failure.