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

Sokos, George; Nikolaidis, Lazaros A.; Mankad, Sunil; Elahi, Dariush; Shannon, Richard P.

doi:10.1016/j.cardfail.2006.08.211

Cited by 598 publications

(425 citation statements)

References 28 publications

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“…While the SAVOR-TIMI 53 trial reported an increased CHF risk with incretin-based drugs, some clinical studies have suggested that incretin-based drugs may play a protective role in the pathogenesis of CHF (22,23). For example, studies demonstrated that B-type natriuretic peptide, a cardiac marker that is elevated in the presence of CHF (24), was decreased in patients treated with liraglutide (25) or exenatide (26).…”

Section: Discussionmentioning

confidence: 99%

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Filion

Azoulay

et al. 2014

Diabetes Care

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OBJECTIVETo determine whether the use of incretin-based drugs, including GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of congestive heart failure (CHF) among patients with type 2 diabetes. RESEARCH DESIGN AND METHODSThe U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, was used to conduct a cohort study with a nested case-control analysis among patients newly prescribed antidiabetic drugs between 1 January 2007 and 31 March 2012 and no prior history of CHF. Case subjects were defined as patients hospitalized for a first CHF and matched with up to 20 control subjects on age, duration of treated diabetes, calendar year, and time since cohort entry. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% CIs of incident CHF comparing current use of incretin-based drugs with current use of two or more oral antidiabetic drugs. RESULTSThe cohort consisted of 57,737 patients followed for a mean 2.4 years, during which time 1,118 incident cases of hospitalized CHF were identified (incidence rate 8.1/1,000 person-years). Current use of incretin-based drugs was not associated with an increased risk of CHF (adjusted OR 0.85 [95% CI 0.62-1.16]). Secondary analyses revealed no duration-response relationship (P trend = 0.39). CONCLUSIONSIn our population-based study, incretin-based drug use was not associated with an increased risk of CHF among patients with type 2 diabetes. These findings provide some reassurance, but will need to be replicated in other large-scale studies.Incretin-based drugs, which consist of dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 analogs, were first approved by the U.S. Food and Drug Administration in 2006 for the treatment of type 2 diabetes. Both DPP-4 inhibitors and GLP-1 analogs improve glycemic control by increasing plasma levels of endogenous and exogenous GLP-1, respectively. This increase in GLP-1 stimulates insulin secretion and inhibits glucagon secretion (1).The cardiovascular safety of incretin-based drugs is currently under debate. This debate stems from a secondary analysis of the randomized controlled trial SAVOR-TIMI 53, in which saxagliptin was associated with an increased risk of congestive heart failure (CHF) (hazard ratio [HR] 1.27 [95% CI 1.07-1.51]) (2). In contrast, the EXAMINE trial found no association between alogliptin and CHF (HR 1.07 [95% CI 0.79-1.46]) (3). A subsequent meta-analysis of randomized controlled trials found an increased risk of CHF with DPP-4 inhibitors (relative risk 1.16 [95% CI 1.01-1.33]) (4), but these results were driven by those of SAVOR-TIMI 53. Although the safety

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Section: Discussionmentioning

confidence: 99%

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Filion

Azoulay

et al. 2014

Diabetes Care

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“…The in-hospital mortality rate and hospital length of stay were reduced (10% vs 27% and 6.1 vs 9.8 days, p<0.02, respectively) in the GLP-1 treated group. Sokos et al 19 was the first group to demonstrate that a long-term infusion of GLP-1 improves both LVEF and functional capacity in human patients with advanced heart failure. In a single-center pilot study, 21 obese patients with LVEF ≤40% and NYHA class III or IV heart failure were divided to receive a continuous subcutaneous infusion of GLP-1 or a small volume of saline as a control over 5 weeks.…”

Section: Experimental Studies Of Glp-1 In Non-ischemic Dilated Cardiomentioning

confidence: 99%

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

Fields

Patterson

Karnik

et al. 2009

Clinical Cardiology

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Pharmacologic intervention for the failing heart has traditionally targeted neurohormonal activation and ventricular remodeling associated with cardiac dysfunction. Despite the multitude of agents available for the treatment of heart failure, it remains a highly prevalent clinical syndrome with substantial morbidity and mortality, necessitating alternative strategies of targeted management. One such area of interest is the ability to modulate myocardial glucose uptake and its impact on cardioprotection. Glucose‐insulin‐potassium (GIK) infusions have been studied for decades, with conflicting results regarding benefit in acute myocardial infarction. Based on the same concepts, glucagon‐like peptide‐1‐[7–36] amide (GLP‐1) has recently been demonstrated to be a more effective alternative in left ventricular (LV) systolic dysfunction. This paper provides a review on the current evidence supporting the use of GLP‐1 in both animal models and humans with ischemic and nonischemic cardiomyopathy. Copyright © 2009 Wiley Periodicals, Inc.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…It will assess the impact of once-weekly exenatide therapy in approximately 14,000 patients, with or without known cardiovascular disease, from heterogeneous practice environments in 35 countries from North and South America, Europe, Africa, Asia, and Australasia.…”

Section: Methodsmentioning

confidence: 99%

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

Holman

Bethel

George

et al. 2016

American Heart Journal

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The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary composite cardiovascular endpoint. EXSCEL is powered to detect a 15% relative risk reduction in the exenatide once weekly group, with 85% power and a 2-sided 5% alpha. The primary safety hypothesis is that exenatide onceweekly is noninferior to usual care with respect to the primary cardiovascular composite endpoint. Noninferiority will be concluded if the upper limit of the confidence interval is <1.30. 4EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broad range of cardiovascular risk. It will also provide longterm safety information on exenatide once-weekly in people with T2DM. ClinicalTrials.gov Identifier: NCT011443385

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

Cited by 598 publications

References 28 publications

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

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

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