Abstract
BackgroundThe effect of glucagon-like peptide-1(GLP-1) receptor agonists on heart failure remains uncertain. We therefore conducted a systematic review to assess the possible impact of GLP-1 agonists on heart failure or hospitalization for heart failure in patients with type 2 diabetes.MethodsWe searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov to identify randomized controlled trials (RCTs) and observational studies that addressed the effect of GLP-1 receptor agonists in adults with type 2 diabetes, and explicitly reported heart failure or hospitalization for heart failure. Two paired reviewers screened reports, collected data, and assessed the risk of bias. We pooled data from RCTs and observational studies separately, and used the GRADE approach to rate the quality of evidence.ResultsWe identified 25 studies that were eligible for our review; 21 RCTs (n = 18,270) and 4 observational studies (n = 111,029). Low quality evidence from 20 RCTs suggested, if anything, a lower incidence of heart failure between GLP-1 agonists versus control (17/7,441 vs. 19/4,317; odds ratio (OR) 0.62, 95 % confidence interval (CI) 0.31 to 1.22; risk difference (RD) 19 fewer, 95 % CI 34 fewer to 11 more per 1000 over 5 years). Three cohort studies comparing GLP-1 agonists to alternative agents provided very low quality evidence that GLP-1 agonists do not increase the incidence of heart failure. One RCT provided moderate quality evidence that GLP-1 agonists were not associated with hospitalization for heart failure (lixisenatide vs placebo: 122/3,034 vs. 127/3,034; adjusted hazard ratio 0.96, 95 % CI 0.75 to 1.23; RD 4 fewer, 95 % CI 25 fewer to 23 more per 1000 over 5 years) and a case–control study provided very low quality evidence also suggesting no association (GLP-1 agonists vs. other anti-hyperglycemic drugs: 1118 cases and 17,626 controls, adjusted OR 0.67, 95 % CI 0.32 to 1.42).ConclusionsThe current evidence suggests that GLP-1 agonists do not increase the risk of heart failure or hospitalization for heart failure among patients with type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0260-0) contains supplementary material, which is available to authorized users.
Highlights
The effect of glucagon-like peptide-1(GLP-1) receptor agonists on heart failure remains uncertain
Glucagon-like peptide-1 (GLP-1) receptor agonists are a relatively new class of incretin-based agents for the treatment of type 2 diabetes mellitus that lower blood glucose [1, 2], reduce body weight [3], and possibly reduce cardiovascular risk compared to placebo [4, 5]
Evidence from randomized controlled trials RCTs reporting heart failure Twenty trials reported on heart failure; 18 (80 %) were multi-center studies, and 18 (90 %) were clearly labeled as phase III trials
Summary
The effect of glucagon-like peptide-1(GLP-1) receptor agonists on heart failure remains uncertain. In 2014, the US Food and Drug Administration raised concerns regarding heart failure risk with one dipeptidyl peptidase-4 (DPP-4) inhibitor, saxagliptin [7] These concerns followed publication of studies that reported increased risk of hospitalization for heart failure in patients using DPP-4 inhibitors [8,9,10]. These observations raise the possibility that GLP-1 agonists, which share a similar pharmacological mechanism with DPP-4 inhibitors, might cause heart failure. Clinical studies suggested that GLP-1 agonists have positive effects on cardiovascular biomarkers, such as high-sensitivity Creactive protein and plasminogen activator inhibitor-1 [12, 13], and improve regional and overall left ventricular function in patients with acute myocardial infarction and severe systolic dysfunction after successful primary angioplasty [14]
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