Glucagon-like peptide-1 receptor agonists and heart failure in type 2 diabetes: systematic review and meta-analysis of randomized and observational studies

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.

Cardiovascular Safety of Incretin-Based Therapies in Type 2 Diabetes: Systematic Review of Integrated Analyses and Randomized Controlled Trials

“…We identified four meta-analyses of GLP-1 receptor agonists for assessment (Table 2) [12, 41, 55, 56]. One meta-analysis of trial-level data reported comparisons between GLP-1 receptor agonists and non-GLP-1 receptor agonists [12].…”

“…Table 4 shows that the GLP-1 receptor agonist drug class and its members were not associated with increasing risk of MACE components, including heart failure, on the basis of results of three meta-analyses [12, 41, 56], although there was evidence associating exenatide with increased risk of arrhythmia (OR 2.83; 95% CI 1.06–7.57) [41]. …”

GLP-1 receptor agonists and heart failure in diabetes

“…Thus, it may be concluded that the effect of liraglutide on LVEF is, if anything, modest and probably not clinically relevant. ; this finding was, however, based on a limited number of events (five in total) and a very wide CI [33]. Nevertheless, these data were confirmed in the second meta-analysis reporting the HR for exenatide, albiglutide and liraglutide (Table 2) [34].…”

“…The effects of GLP-1RAs on the risk of developing HF in patients with T2D have been analyzed by two large metaanalyses of phase-II/III randomized controlled trials (RCTs; Table 2) [33,34]. The first meta-analysis provided data for all the GLP-1RAs combined and for each individual GLP-1RA (albiglutide, dulaglutide, exenatide and liraglutide) [33].…”

“…The first meta-analysis provided data for all the GLP-1RAs combined and for each individual GLP-1RA (albiglutide, dulaglutide, exenatide and liraglutide) [33]. When considering all 20 pooled trials, the risk of HF was lower with GLP-1RAs than with the comparators [hazard …”