Effects of Glucagon-Like Peptide-1 in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction After Successful Reperfusion

Abstract

Background-Glucose-insulin-potassium infusions are beneficial in uncomplicated patients with acute myocardial infarction (AMI) but are of unproven efficacy in AMI with left ventricular (LV) dysfunction because of volume requirements associated with glucose infusion. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties that stimulate glucose uptake without the requirements for concomitant glucose infusion. Methods and Results-We investigated the safety and efficacy of a 72-hour infusion of GLP-1 (1.5 pmol/kg per minute) added to background therapy in 10 patients with AMI and LV ejection fraction (EF) Ͻ40% after successful primary angioplasty compared with 11 control patients. Echocardiograms were obtained after reperfusion and after the completion of the GLP-1 infusion. Baseline demographics and background therapy were similar, and both groups had severe LV dysfunction at baseline (LVEFϭ29Ϯ2%

Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial

“…31,32 Further cardioprotective effects, by means of increased coronary flow, 29 reduced myocardial infarct size, 33 and improved left ventricular function, have also been suggested by animal data. 30,34 Human mechanistic studies are consistent with these findings demonstrating an improvement in flow-mediated vasodilation in the postprandial state, 13 reduced infarct size in patients with ST-segment elevation myocardial infarction, 12,14 and an improvement in left ventricular ejection fraction in patients with heart failure. 35 These data together justify the conduct of a large-scale, adequately powered outcome trial testing for the superiority of a diabetes treatment regimen containing once-weekly exenatide on cardiovascular outcomes.…”

“…[7][8][9][10][11] Mechanistic data suggest that exenatide can improve cardiac function in patients with chronic heart failure, 12 improve endothelial dysfunction, 13 and reduce infarct size after ST-segment elevation myocardial infarction. 12,14 A patient-level integrated meta-analysis showed no evidence for increased cardiovascular disease risk with use of exenatide in 6 subjects with T2DM, 15 while a retrospective analysis of a medical and pharmaceutical insurance claims database found a lower relative cardiovascular disease risk associated with exenatide treatment than with other glucose-lowering drugs. 16 A small increase in heart rate has been observed with GLP-1 receptor agonists, which appears to be a class effect.…”

GLP-1 receptor agonists and heart failure in diabetes

“…Mild improvements were observed in some studies [26,27], whereas no significant changes in LVEF were noted in others [28,29] (Table 1).…”

Coronary Artery Disease and Diabetes Mellitus

“…27 Newer antidiabetic agents, such as, agonists of the glucagon-like peptide-1 (GLP1) receptor or dipeptidyl peptidase 4 (DPP4) inhibitors, which prevent the breakdown of endogenous GLP1, have shown beneficial effects in patients undergoing angioplasty and CABG in small studies. 28,29 However, in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR), the DPP-4 inhibitor saxagliptin did not change the primary composite endpoint of cardiovascular death, myocardial infarction, or ischemic stroke, when added to the standard of care in patients at high risk for cardiovascular events. 30 Although saxagliptin clearly met the FDA guidance for cardiovascular safety, therapy with the drug was associated with an unexpected increased risk of hospitalization for heart failure (especially in patients with high baseline BNP levels) and a higher frequency of hypoglycemia.…”