Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Events: A Meta-Analysis of Randomized Clinical Trials

Monami, Matteo; Cremasco, Francesco; Lamanna, Caterina; Colombi, Claudia; Desideri, Carla Maria; Iacomelli, Iacopo; Marchionni, Niccolò; Mannucci, Edoardo

doi:10.1155/2011/215764

Cited by 90 publications

(74 citation statements)

References 47 publications

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“…A meta-analysis of 36 trials with a duration ≥12 weeks showed that the MantelHaenszel OR (MH-OR) for major cardiovascular events versus placebo or other comparators was 0.74 for all GLP-1 receptor agonists (95% CI: 0.50-1.08, p = 0.12), 0.85 for exenatide (95% CI: 0.50-1.45, p = 0.55) and 0.69 for liraglutide (95% CI: 0.40-1.22, p = 0.20) [92]. Specifically designed long-term trials are currently assessing the cardiovascular effects of GLP-1 receptor agonists.…”

Section: Cardiovascular Systemmentioning

confidence: 97%

Adverse Effects of GLP-1 Receptor Agonists

2014

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■ AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.

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Section: Cardiovascular Systemmentioning

confidence: 97%

Adverse Effects of GLP-1 Receptor Agonists

2014

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“…In a recently updated meta-analysis of 53 trials, DPP-4 inhibitors were associated with a reduced risk of major cardiovascular events (OR = 0.689; 0.528, 0.899; p = 0.006) compared with placebo or other active treatments [39]. Despite positive cardiovascular effects reported with exenatide or liraglutide [16,40], a similar metaanalysis of 36 trials with exenatide and liraglutide showed a similar trend for a reduction in the incidence of major cardiovascular adverse events, although the difference was not significant versus placebo or active comparators (OR = 0.74; 0.50, 1.08; p = 0.12) [41]. Thus, current data do not support a superiority of GLP-1 receptor agonists over DPP-4 inhibitors regarding potential cardiovascular protection.…”

Section: Clinical Outcomesmentioning

confidence: 96%

Dipeptidylpeptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) receptor agonists: Yes

Scheen

2012

European Journal of Internal Medicine

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The pharmacological treatment of type 2 diabetes (T2DM) is becoming increasingly complex, especially since the availability of incretin-based therapies. Compared with other glucose-lowering strategies, these novel drugs offer some advantages such as an absence of weight gain and a negligible risk of hypoglycaemia and, possibly, better cardiovascular and β-cell protection. The physician has now multiple choices to manage his/her patient after secondary failure of metformin, and the question whether it is preferable to add an oral dipeptidylpeptidase-4 (DPP-4) inhibitor (gliptin) or an injectable glucagon-like peptide-1 (GLP-1) receptor agonist will emerge. Obviously, DPP-4 inhibitors offer several advantages compared with GLP-1 receptor agonists, especially regarding easiness of use, tolerance profile and cost. However, because they can only increase endogenous GLP-1 concentrations to physiological (rather than pharmacological) levels, they are less potent to improve glucose control, promote weight reduction ("weight neutrality") and reduce blood pressure compared to GLP-1 receptor agonists. Of note, none of the two classes have proven long-term safety and positive impact on diabetic complications yet. The role of DPP-4 inhibitors and GLP-1 receptor agonists in the therapeutic armamentarium of T2DM is rapidly evolving, but their respective potential strengths and weaknesses should be better defined in long-term head-to-head comparative controlled trials. Instead of trying to answer the question whether DPP-4 inhibitors are favourable to GLP-1 receptor agonists (or vice versa), it is probably more clinically relevant to look at which T2DM patient will benefit more from one or the other therapy considering all his/her individual clinical characteristics ("personalized medicine").

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“…The results exclude, at least in the short term, any increase in CV morbidity and mortality in comparison with placebo or other active drugs. 134,147,148 Besides, placebo-controlled trials have demonstrated that patients treated with GLP-1 RA have a lower incidence of MACE, CV mortality and all-cause mortality.…”

Section: Glucagon-like Peptide-1 Receptor Agonistsmentioning

confidence: 99%

Cardiovascular safety of type 2 diabetes medications: Review of existing literature and clinical implications

Paredes¹,

Matta-Coelho²,

Monteiro³

et al. 2016

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Type 2 diabetes mellitus (T2DM), cardiovascular disease (CvD) and the cardiovascular effect of antidiabetic drugs are today critical medical issues, with the prevalence of T2DM in particular showing a steep increase worldwide, mainly due to unhealthy lifestyle habits. T2DM in association with obesity and other cardiovascular risk factors, results in the development of CvD, the leading cause of morbidity and mortality in patients with T2DM. Thus, treatment of T2DM is an individualized and complex challenge in which targeting cardiovascular risk factors is an important component in the decision making. given the cardiovascular adverse events associated with rosiglitazone, both the food and Drug Administration and the european Medicines Agency currently require the demonstration of cardiovascular safety of new antidiabetic drugs. Consequently, clinical trials to guarantee their cardiovascular safety are now obligatory. This review aims to summarize the available evidence on the cardiovascular effects and safety of the major drugs used in T2DM treatment and also to provide an overview of upcoming and ongoing clinical trials in this field. Our belief is that this review will be of substantial assistance to all medical doctors who are treating diabetic patients, namely primary care physicians, internal medicine doctors, endocrinologists, diabetologists and less well experienced personnel such as young doctors in training.

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Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Events: A Meta-Analysis of Randomized Clinical Trials

Cited by 90 publications

References 47 publications

Adverse Effects of GLP-1 Receptor Agonists

Adverse Effects of GLP-1 Receptor Agonists

Dipeptidylpeptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) receptor agonists: Yes

Cardiovascular safety of type 2 diabetes medications: Review of existing literature and clinical implications

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