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

Objective. Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists.Design and Methods. MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration ≥12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events.Results. Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50–1.08),P=.12(0.85 (0.50–1.45),P=.55, and 0.69 (0.40–1.22),P=.20, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25–0.83),P=.009, and 1.05 (0.63–1.76),P=.84, respectively.Conclusions. To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect.

Download Full-text

Glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized clinical trials

Acta Endocrinologica ◽

10.1530/eje-09-0101 ◽

2009 ◽

Vol 160 (6) ◽

pp. 909-917 ◽

Cited By ~ 94

Author(s):

Matteo Monami ◽

Niccolò Marchionni ◽

Edoardo Mannucci

Keyword(s):

Type 2 Diabetes ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Relevant Information ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

ObjectiveThe role of glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes is debated; many recent trials, which were not included in previous meta-analyses, could add relevant information.Design and methodsAll available randomized controlled trials (RCTs), either published or unpublished, performed in type 2 diabetic patients with GLP-1 receptor agonists (exenatide and liraglutide), with a duration>12 weeks were meta-analysed for HbA1c, body mass index, hypoglycaemia and other adverse events.Results and conclusionsA total of 21 RCTs (six of which unpublished), enrolling 5429 and 3053 patients (with GLP-1 receptor agonists and active comparator or placebo respectively), was retrieved and included in the analysis. GLP-1 receptor agonists determine a significant improvement of HbA1c in comparison with placebo (−1.0 (−1.1, −0.8),P<0.001), with a low risk of hypoglycaemia. There is no evidence of increased cardiovascular risk with the use of GLP-1 receptor agonists. GLP-1 receptor agonists, which induce weight loss, are associated with gastrointestinal side effects. GLP-1 receptor agonists are effective in reducing HbA1c and postprandial glucose. In patients failing to sulphonylureas and/or metformin, GLP-1 receptor agonists are similarly effective as insulin. Available data suggest that the efficacy and tolerability of the novel agent, liraglutide, which is adequate for once-a-day administration, are comparable with those of exenatide bis in die.

Download Full-text

The Efficacy and Tolerability of Exenatide in Comparison to Placebo; A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3g883 ◽

2011 ◽

Vol 15 (1) ◽

pp. 1 ◽

Cited By ~ 17

Author(s):

Shekoufeh Nikfar ◽

Mohammad Abdollahi ◽

Pooneh Salari

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

New Drugs ◽

Diabetic Patients ◽

Serum Triglycerides ◽

Study Duration

Recent investigations in finding new drugs in the treatment of diabetes have led to the discovery of several pathological pathways involved in diabetes. Exenatide a drug with incretin mimetic activity was studied in several in vivo and in vitro as well as human studies. It has shown promising results in controlling metabolic indices in type-2 diabetes and was approved by FDA but still there is an active safety alert on it. In this study we aimed to meta-analyze all placebo-controlled clinical trials on the efficacy or tolerability of exenatide in type 2 diabetes. The literature search provided 1016 articles while only 14 articles were eligible to be included in the meta-analysis with a total of 2583 patients enrolled in the study. According to the wide variation in design of various studies, the study duration of 16 weeks and less or more and dose (5 μg bid versus 10 μg bid) were considered and analyzed. The results of this meta-analysis show that exenatide decreases fasting plasma glucose and HbA1C significantly regardless of dose and study duration. The effect of exenatide on weight reduction was more prominent at the dose of 10 μg bid regardless of the study duration, however at the dose of 5 μg bid, significant results were observed after drug administration for more than 16 weeks. Exenatide usage decreased serum triglycerides indifferent to dose and study duration while its effect on cholesterol was not prominent. Along with these impacts, exenatide changed LDL and HDL cholesterol at the lower dose. The hemodynamic effect of exenatide was observed as significant decrements in systolic and diastolic blood pressure at the higher dose. The risk of nausea, vomiting and hypoglycemia was significant and indifferent to dose while headache and nasopharyngaitis were seen more at lower dose. It is concluded that exenatide can be considered as a good hypoglycemic agent in type-2 diabetic patients with benefits on lipid profile and blood pressure with partially questionable tolerability. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Download Full-text