Adverse effects of incretin‐based therapies on major cardiovascular and arrhythmia events: meta‐analysis of randomized trials

Wang, Tiansheng; Wang, Fei; Zhou, Junwen; Tang, Huilin; Giovenale, Sharon

doi:10.1002/dmrr.2804

Cited by 27 publications

(18 citation statements)

References 131 publications

(169 reference statements)

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“… Sulphonylureas Hypoglycaemia risk, weight gain [ 78 ], cardiovascular disease [ 79 ]. Incretin-based therapies Arrhythmia [ 80 ], pancreatitis [ 81 ]. Thiazolidinediones Risk of heart failure [ 82 ].…”

Section: Introductionmentioning

confidence: 99%

Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

et al. 2017

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BackgroundZinc is a metal ion that is essential for growth and development, immunity, and metabolism, and therefore vital for life. Recent studies have highlighted zinc’s dynamic role as an insulin mimetic and a cellular second messenger that controls many processes associated with insulin signaling and other downstream pathways that are amendable to glycemic control.Main bodyMechanisms that contribute to the decompartmentalization of zinc and dysfunctional zinc transporter mechanisms, including zinc signaling are associated with metabolic disease, including type 2 diabetes. The actions of the proteins involved in the uptake, storage, compartmentalization and distribution of zinc in cells is under intense investigation. Of these, emerging research has highlighted a role for several zinc transporters in the initiation of zinc signaling events in cells that lead to metabolic processes associated with maintaining insulin sensitivity and thus glycemic homeostasis.ConclusionThis raises the possibility that zinc transporters could provide novel utility to be targeted experimentally and in a clinical setting to treat patients with insulin resistance and thus introduce a new class of drug target with utility for diabetes pharmacotherapy.

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Section: Introductionmentioning

confidence: 99%

Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

et al. 2017

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“…The potential cardioprotective effects of incretin-based therapies were shown in several studies 9 – 12 . Although numerous meta-analyses have been conducted to assess the cardiovascular safety of GLP-1 agonists and DPP-4 inhibitors, inconsistent results were report from different reviews, and the long-term outcomes were limited 13 – 16 . A recent meta-analysis suggest that use of exenatide and saxagliptin may increase the risk of arrhythmia and heart failure, respectively 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Although numerous meta-analyses have been conducted to assess the cardiovascular safety of GLP-1 agonists and DPP-4 inhibitors, inconsistent results were report from different reviews, and the long-term outcomes were limited 13 – 16 . A recent meta-analysis suggest that use of exenatide and saxagliptin may increase the risk of arrhythmia and heart failure, respectively 13 . However, other studies did not demonstrate any differences on cardiovascular risk in comparison with other antidiabetic agents or placebo 14 – 16 .…”

Section: Introductionmentioning

confidence: 99%

Effect of Long-term Incretin-Based Therapies on Ischemic Heart Diseases in Patients with Type 2 Diabetes Mellitus: A Network Meta-analysis

Chang

Yang

Wang

et al. 2017

Sci Rep

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Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up. The network meta-analysis was performed using R Software with a GeMTC package. A total of 40 trials were included. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 agonists were associated with a lower risk of myocardial infarction (MI) than were sulfonylureas (odds ratio [95% credible interval] 0.41 [0.24–0.71] and 0.48 [0.27–0.91], respectively). These results suggested that patients with T2DM receiving long-term incretin-based therapies have a lower risk of MI than do those receiving sulfonylurea-based therapy. These findings highlight the risks of cardiovascular events in patients who receive long-term incretin-based therapies, and may provide evidence for the selection of antidiabetic therapy in the future.

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“…; 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]. In two other metaanalyses specifically dedicated to either albiglutide [35] or dulaglutide [36], neither reported any significantly increased risk of hospitalization for HF ( Table 2).…”

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 84%

“…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].…”

Section: Glp-1ras and Heart Failure Riskmentioning

confidence: 99%

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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Adverse effects of incretin‐based therapies on major cardiovascular and arrhythmia events: meta‐analysis of randomized trials

Cited by 27 publications

References 131 publications

Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

Effect of Long-term Incretin-Based Therapies on Ischemic Heart Diseases in Patients with Type 2 Diabetes Mellitus: A Network Meta-analysis

GLP-1 receptor agonists and heart failure in diabetes

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