Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction

Margulies, Kenneth B.; Hernandez, Adrian F.; Redfield, Margaret M.; Givertz, Michael M.; Oliveira, Guilherme H.; Cole, Robert T.; Mann, Douglas L.; Whellan, David J.; Kiernan, Michael S.; Felker, G. Michael; McNulty, Steven E.; Anstrom, Kevin J.; Shah, Monica; Braunwald, Eugene; Cappola, Thomas P.

doi:10.1001/jama.2016.10260

Cited by 504 publications

(381 citation statements)

References 21 publications

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“…Similarly, no significant between-group differences were reported for the different exploratory secondary endpoints (primary endpoint components plus cardiac structure and function, 6-min walk test, quality of life and combined events). In addition, prespecified subgroup analyses restricted to only patients with T2D failed to reveal any significant between-group differences [45]. Thus, in patients recently hospitalized for HF and a reduced LVEF, the use of liraglutide did not lead to greater post-hospitalization clinical stability.…”

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 88%

“…Several studies have investigated the effects of liraglutide on cardiac function in patients with or without diabetes, and with either coronary heart disease (with preserved LVEF) [40][41][42] or CHF and reduced LVEF (< 40%) [43][44][45]. The results were widely heterogeneous.…”

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 99%

“…Indeed, three studies reported a significant increase in LVEF in patients with preserved LVEF [40,41] and reduced LVEF [43], whereas three other studies -one in patients with preserved cardiac function [42] and two in patients with altered function [44,45] -reported almost no changes in LVEF with liraglutide compared with a placebo (Table 3). The two largest trials, with follow-ups of about 6 months, also reported virtually no changes in LVEF [44,45]. Thus, it may be concluded that the effect of liraglutide on LVEF is, if anything, modest and probably not clinically relevant.…”

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 99%

“…The Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) study has tested the hypothesis that sustained therapy with liraglutide (up-titrated to 1.8 mg), initiated within 14 days of hospitalization for an acute HF syndrome (despite already receiving evidence-based therapies, including furosemide), is associated with greater clinical stability throughout 180 days in patients with or without T2D, and with advanced HF and reduced LVEF (≤ 40%) [45]. The primary endpoint was a global score in which patients were ranked across three hierarchical tiers: time to death; time to rehospitalization for HF; and time-averaged proportional change in N-terminal pro-BNP levels from baseline to 180 days.…”

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 99%

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GLP-1 receptor agonists and heart failure in diabetes

Scheen

2017

Diabetes & Metabolism

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The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR -TIMI 53), whereas a markedly decreased risk was highlighted with the sodium -glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet, the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial function remain controversial. Whereas some promising observations have been reported in various animal models, the effects of GLP-1RAs on myocardial function in humans are more heterogeneous, while the positive effect on left ventricular ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in most patients with HF. However, no increased risk of hospitalization for HF has been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide, albiglutide, dulaglutide, liraglutide), demonstrating the safety of this pharmacological class, and such findings have been confirmed by three large prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a trend towards a reduction in HF hospitalization (-13%, P = 0.14), together with a significant reduction in cardiovascular and all-cause mortality in patients with T2D at risk of cardiovascular disease. These results are reassuring in the face of the somewhat negative results of the FIGHT trial, which evaluated the effects of liraglutide in patients with advanced HF and low LVEF, such that further studies and caution are now required when using this agent to treat such patients in clinical practice.

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Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 88%

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 99%

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 99%

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 99%

See 2 more Smart Citations

GLP-1 receptor agonists and heart failure in diabetes

Scheen

2017

Diabetes & Metabolism

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“…In the Functional Impact of GLP‐1 for Heart Failure Treatment (FIGHT) trial, liraglutide did not improve cardiac function in participants with an EF of <25% 19. In the liraglutide on left ventricular function (LIVE) trial, liraglutide did improve diastolic function as indicated by E/e′ in participants with an EF of <45% 20.…”

Section: Discussionmentioning

confidence: 99%

Liraglutide relieves cardiac dilated function than DPP‐4 inhibitors

Hiramatsu

Asano

Mabuchi

et al. 2018

Eur J Clin Investigation

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IntroductionDiabetes mellitus is a progressive disease with cardiovascular complications. This study evaluated the effects of liraglutide, a glucagon‐like peptide‐1 analogue and the dipeptidyl peptidase 4 inhibitors sitagliptin and linagliptin on cardiac function in type 2 diabetes patients with renal impairment.Materials and MethodsA total of 139 patients who were referred because of suboptimal glycaemic control were randomly assigned to liraglutide 0.9 mg/d (n = 45), sitagliptin 50 mg/d, (n = 49) or linagliptin 5 mg/d (n = 45) at enrolment and were evaluated. Blood glucose, glycosylated haemoglobin and serum creatinine were assayed every 3 months for 48 months. Echocardiography was performed every 12 months for 48 months.ResultsCompared with baseline, fasting glucose, postprandial glucose, and systolic and diastolic pressure, but not estimated glomerular filtration rate, significantly decreased in all three groups. Albuminuria decreased from 24 to 48 months with liraglutide, but only from 24 to 30 months with sitagliptin and linagliptin. Diastolic function, assessed by E/e′ or left atrial dimension improved only with liraglutide.ConclusionsLiraglutide was effective for glucose and blood pressure control, reduced albuminuria and improved diastolic function. Diastolic function was not improved by sitagliptin and linagliptin.

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