June 1, 2018Open Access
Potentiation of Insulin Signaling Contributes to Heart Failure in Type 2 Diabetes
Key Result
Antihyperglycemic drugs acting through insulin signaling increase heart failure risk, whereas drugs ameliorating hyperinsulinemia without insulin signaling reduce this risk.
Structured PICO
Do antihyperglycemic drugs that act through insulin signaling increase the risk of heart failure in patients with type 2 diabetes?
P
Population
Patients with type 2 diabetes
I
Intervention
Antihyperglycemic drugs (sulfonylureas, thiazolidinediones, incretins, metformin, and sodium-glucose cotransporter 2 inhibitors)
O
Outcome
Risk or clinical course of heart failure
Antihyperglycemic therapies that avoid potentiating insulin signaling, such as metformin and SGLT2 inhibitors, may be preferable for mitigating heart failure risk in type 2 diabetes.
Abstract
The heightened risk of heart failure in type 2 diabetes cannot be explained by the occurrence of clinically overt myocardial ischemic events or hyperglycemia. Experimentally, insulin exerts detrimental effects on the heart, vasculature, kidneys, and adipose tissue that can lead to heart failure. In both randomized clinical trials and observational studies, antihyperglycemic drugs that act through insulin signaling (i.e., sulfonylureas, thiazolidinediones, and incretins) increase the risk or worsen the clinical course of heart failure, whereas drugs that ameliorate hyperinsulinemia and do not signal through insulin (i.e., metformin and sodium-glucose cotransporter 2 inhibitors) reduce the risk of heart failure.