Effects of incretin-based therapy in patients with heart failure and myocardial infarction.
Studies designed to evaluate the short-term effects of incretin-related drugs in subjects with cardiac disease are still preliminary. In patients with heart failure, two of five studies showed that glucagon-like peptide-1 (GLP-1) infusion was associated with an absolute increase in left ventricular ejection fraction (LVEF) by 6-10 %, whereas no significant benefit was observed in the remaining three studies. In patients with coronary artery disease, single infusion of the GLP-1 receptor analog, exenatide, did not increase LVEF, but this drug may decrease infarct size in patients with myocardial infarction presenting with short duration of ischemic symptoms. Single dose of GLP-1 and the dipeptidyl-peptidase-IV (DPP-IV) inhibitor, sitagliptin, may improve left ventricular function, predominantly in ischemic segments, and attenuate post-ischemic stunning. Nausea, vomiting and hypoglycemia were the most common adverse effects associated with GLP-1 and exenatide administration. Increased heart rate was also observed with exenatide in patients with heart failure. Large randomized trials including diabetic patients with preexisting heart failure and myocardial infarction showed that chronic therapy with the DPP-IV inhibitors saxagliptin and alogliptin did not reduce cardiovascular events or mortality. Moreover, saxagliptin use was associated with significant increase in frequency of heart failure requiring hospitalization, hypoglycemia and angioedema. Overall, short-term preliminary data suggest potential cardioprotective effects of exenatide and sitagliptin in patients with heart failure and myocardial infarction. Meanwhile, long-term randomized trials suggest no benefit of alogliptin, and increased harm associated with the use of saxagliptin.
Endocrinology Division, OliveView-UCLA Medical Center, David-Geffen School of Medicine, 14445 Olive View Dr, Sylmar, 91342, CA, USA, nmikhail@dhs.lacounty.gov.
Nasser
N
Mikhail
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D054795:Incretins / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use; D014688:Venoms / Q000627:therapeutic use
D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D054795:Incretins; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide