Elsevier

Journal of Cardiac Failure

Volume 12, Issue 9, December 2006, Pages 694-699
Journal of Cardiac Failure

Clinical Investigation
Glucagon-Like Peptide-1 Infusion Improves Left Ventricular Ejection Fraction and Functional Status in Patients With Chronic Heart Failure

https://doi.org/10.1016/j.cardfail.2006.08.211Get rights and content

Abstract

Background

Insulin resistance is present in the setting of congestive heart failure. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties.

Methods and Results

We investigated the safety and efficacy of a 5-week infusion of GLP-1 (2.5 pmol/kg/min) added to standard therapy in 12 patients with New York Heart Association class III/IV heart failure and compared the results with those of 9 patients with heart failure on standard therapy alone. Echocardiograms, maximum myocardial ventilation oxygen consumption (VO2 max), 6-minute walk test, and Minnesota Living with Heart Failure quality of life score (MNQOL) were assessed. Baseline demographics, background therapy, and the degree of left ventricular dysfunction were similar between groups. GLP-1 significantly improved left ventricular ejection fraction (21 ± 3% to 27 ± 3% P < .01), VO2 max (10.8 ± .9 ml/O2/min/kg to 13.9 ± .6 ml/O2/min/kg; P < .001), 6-minute walk distance (232 ± 15 m to 286 ± 12 m; P < .001) and MNQOL score (64 ± 4 to 44 ± 5; P < .01). Benefits were seen in both diabetic and non-diabetic patients. There were no significant changes in any of the parameters in the control patients on standard therapy. GLP-1 was well tolerated with minimal episodes of hypoglycemia and gastrointestinal side effects.

Conclusion

Chronic infusion of GLP-1 significantly improves left ventricular function, functional status, and quality of life in patients with severe 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)

  • H. Taegtmeyer et al.

    Adaptation and maladaptation of the heart in diabetes: part I: general concepts

    Circulation

    (2002)
  • H. Taegtmeyer

    Switching metabolic genes to build a better heart

    Circulation

    (2002)
  • N. Suskin et al.

    Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure

    Eur Heart J

    (2000)
  • L. Amato et al.

    Congestive heart failure predicts the development of non-insulin-dependent diabetes mellitus in the elderly. The Osservatorio Geriatrico Regione Campania Group

    Diabetes Metab

    (1997)
  • A.J. Coats et al.

    Insulin resistance in chronic heart failure

    J Cardiovasc Pharmacol

    (2000)
  • Cited by (0)

    This work was supported originally by Restoragen, Inc., and subsequently by The Pittsburgh Foundation.

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