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

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) <40% 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 (LVEF=29±2%). GLP-1 significantly improved LVEF (from 29±2% to 39±2%, P <0.01), global wall motion score indexes (1.94±0.11→1.63±0.09, P <0.01), and regional wall motion score indexes (2.53±0.08→2.02±0.11, P <0.01) compared with control subjects. The benefits of GLP-1 were independent of AMI location or history of diabetes. GLP-1 was well tolerated, with only transient gastrointestinal effects. Conclusions—When added to standard therapy, GLP-1 infusion improved regional and global LV function in patients with AMI and severe systolic dysfunction after successful primary angioplasty.

[1]  N. Reichek,et al.  Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. , 1989, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[2]  H. Taegtmeyer,et al.  Metabolic support for the postischaemic heart , 1995, The Lancet.

[3]  J. Holst,et al.  Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7–36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships , 1995, Diabetologia.

[4]  J. Habener,et al.  The glucagon-like peptides. , 1999, Endocrine reviews.

[5]  H. Taegtmeyer,et al.  Glucose-insulin-potassium in acute myocardial infarction: the time has come for a large, prospective trial. , 1997, Circulation.

[6]  K. Kent,et al.  Metabolic support during coronary reperfusion. , 1987, American heart journal.

[7]  L. Piegas,et al.  Metabolic Modulation of Acute Myocardial Infarction The ECLA Glucose-Insulin-Potassium Pilot Trial , 1998 .

[8]  C. Apstein Glucose-insulin-potassium for acute myocardial infarction: remarkable results from a new prospective, randomized trial. , 1998, Circulation.

[9]  D. Yellon,et al.  Insulin therapy as an adjunct to reperfusion after acute coronary ischemia: a proposed direct myocardial cell survival effect independent of metabolic modulation. , 2003, Journal of the American College of Cardiology.

[10]  L. Opie Proof that glucose-insulin-potassium provides metabolic protection of ischaemic myocardium? , 1999, The Lancet.

[11]  Felix Zijlstra,et al.  Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial. , 2003, Journal of the American College of Cardiology.

[12]  G. Billman,et al.  Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. , 2003, Circulation.

[13]  S. Kahn,et al.  Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. , 1994, The Journal of clinical investigation.

[14]  J Herlitz,et al.  Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. , 1995, Journal of the American College of Cardiology.

[15]  K. Beatt,et al.  Glucose-insulin-potassium in acute myocardial infarction , 1999, The Lancet.

[16]  L. Rydén,et al.  Glucagon-like peptide-1 (7–36) amide prevents the accumulation of pyruvate and lactate in the ischemic and non-ischemic porcine myocardium , 2003, Peptides.