Clinical InvestigationGlucagon-Like Peptide-1 Infusion Improves Left Ventricular Ejection Fraction and Functional Status in Patients With Chronic Heart Failure
Section snippets
Methods
This was a single-center, open-label, nonrandomized pilot study, designed to evaluate the safety and clinical efficacy of GLP-1 (7–36) amide (Restoragen, Inc., Lincoln, NE) at a dose of 2.5 pmol/kg/min in a group of patients with chronic heart failure. The study was approved by the Investigational Review Board of Allegheny General Hospital and was initially intended to be a 10-week dose escalation study but initial evaluation indicated no additional benefit to higher doses.
To be included,
Results
The demographics of the study groups are depicted in Table 1. The majority of subjects were older patients with NYHA class III heart failure. There were more patients with diabetes and ischemic cardiomyopathy in the GLP-1-treated group (67%) compared with control subjects (56%), although the difference was not significant (P = .95). Fasting glucose levels and HgbA1C levels were higher in the GLP-1-treated patients compared with the control group. Patients in both groups were obese with average
Discussion
We report the hemodynamic and metabolic benefits of a novel insulinotropic and insulinomimetic agent, GLP-1, in patients with severe CHF. We observed significant improvements in both LVEF and functional status. The improvement in LVEF in the GLP-1-treated patients could not be accounted for by changes in blood pressure and was observed in patients with and without diabetes. The enhanced insulin responses resulted in reductions in NEFA and glucose.
The effects of GLP-1 in humans with type 2
Conclusion
GLP-1, an insulinotropic and insulinomimetic peptide, improves LVEF and functional status in patients with systolic heart failure. The safety and benefits are seen in both diabetic and non-diabetic patients. These results warrant further study in a large double-blind randomized trial of patients with advanced heart failure.Table 2.
References (31)
- et al.
Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure
Metabolism
(1991) - et al.
Prognostic importance of insulin-mediated glucose uptake in aged patients with congestive heart failure secondary to mitral and/or aortic valve disease
Am J Cardiol
(1999) - et al.
Insulin resistance in idiopathic dilated cardiomyopathy: a possible etiologic link
J Am Coll Cardiol
(2004) - et al.
Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure
J Am Coll Cardiol
(1997) - et al.
Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial
J Am Coll Cardiol
(2003) - et al.
The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7–37) in normal and diabetic subjects
Regul Pept
(1994) - et al.
Recommendations for the evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography
J Am Soc Echocardiogr
(2003) - et al.
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology
J Am Soc Echocardiogr
(2005) - et al.
Glucagon-like peptide-1 (7–36) amide prevents the accumulation of pyruvate and lactate in the ischemic and non-ischemic porcine myocardium
Peptides
(2003) Heart Disease and Stroke Statistics—2004 Update
(2005)
Adaptation and maladaptation of the heart in diabetes: part I: general concepts
Circulation
Switching metabolic genes to build a better heart
Circulation
Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure
Eur Heart J
Congestive heart failure predicts the development of non-insulin-dependent diabetes mellitus in the elderly. The Osservatorio Geriatrico Regione Campania Group
Diabetes Metab
Insulin resistance in chronic heart failure
J Cardiovasc Pharmacol
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This work was supported originally by Restoragen, Inc., and subsequently by The Pittsburgh Foundation.