Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials

Nreu, Besmir; Dicembrini, Ilaria; Tinti, Federico; Sesti, Giorgio; Mannucci, Edoardo; Monami, Matteo

doi:10.1016/j.numecd.2020.03.013

Cited by 54 publications

(39 citation statements)

References 64 publications

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“…In this study, we found that there is not enough reason to support the use of liraglutide in patients with HF, which is consistent with the latest updated meta-analysis of 43 randomized controlled trials [11]. Another a network meta-analysis of 171,253 participants from 91 randomized controlled trials also showed that GLP-1 analogue was significantly inferior to sodium-glucose co-transporters 2 inhibitors in terms of HF risk [12].…”

supporting

confidence: 77%

Liraglutide in the treatment of heart failure: insight from FIGHT and LIVE

Liang

2020

Cardiovasc Diabetol

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There are many glucose-lowering agents used in patients with heart failure, showing mixed results, this study was conducted to determine the effect of liraglutide, a glucagon-like peptide-1 analogue, on the treatment of patients with heart failure. Patients from the FIGHT and LIVE trials were included, all overlapped data were summarized and described. No significant changes from baseline in left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, hemoglobin A1c, heart rate, left ventricular end-systolic volume index, left ventricular end-diastolic volume index, and 6 min walk test were observed in FIGHT. In LIVE, liraglutide significantly decreased hemoglobin A1c and inceased 6 min walk test and increased heart rate and serious cardiac adverse events, and there were no statistical differences in left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, left ventricular end-systolic volume index, and left ventricular end-diastolic volume index. In this study, we found that there is not enough reason to support the use of liraglutide in patients with heart failure, and importantly, the safety of liraglutide in this particular population remains uncertain. Enhanced recognition the risks and benefits of liraglutide would help guide therapeutic decisions in patients with heart failure.

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supporting

confidence: 77%

Liraglutide in the treatment of heart failure: insight from FIGHT and LIVE

Liang

2020

Cardiovasc Diabetol

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“…First, semaglutide versus control reduced the risk of total SAEs by 8% (RR 0.92) and atrial fibrillation by 31% (RR 0.69), and showed the reduced trend in the risk of septic shock; whereas semaglutide increased the risk of deep vein thrombosis by 266% (RR 3.66), and showed the increased trend in the risk of ventricular tachycardia. An updated meta-analysis [22] found that incorporative GLP1RAs did not increase the risk of atrial fibrillation, but failed to assess individual GLP1RAs. In this study we revealed a GLP1RA semaglutide with a 31% reduction in the risk of atrial fibrillation.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials

et al. 2021

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The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I 2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I 2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I 2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I 2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

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“…To summarize several meta-analyses of CVOTs conducted with GLP-1RAs, it isconfirmed that based on 43 trials, GLP-1RAs are a class of efficacious agent for reducing MACE (MH-OR 0.87 [0.83, 0.92]), cardiovascular and all-cause mortality (MH-OR 0.89 [0.83, 0.96]) [48]. Further, GLP-1RAs significantly reduce the risk of MI and stroke, but have a neutral effect on hospitalization for heart failure upon 5 available CVOTs [49].…”

Section: Chronic Kidney Disease (Ckd)mentioning

confidence: 99%

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

120

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Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.

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Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials

Cited by 54 publications

References 64 publications

Liraglutide in the treatment of heart failure: insight from FIGHT and LIVE

Liraglutide in the treatment of heart failure: insight from FIGHT and LIVE

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

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