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

Unit of Geriatric Medicine, Department of Critical Care Medicine, University of Florence and Azienda Ospedaliera Careggi, Florence, Italy

(Correspondence should be addressed to E Mannucci who is now at Section of Geriatric Cardiology, Department of Cardiovascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50141 Florence, Italy; Email: edoardo.mannucci{at}unifi.it)

Objective: The 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Design and methods: All available randomized controlled trials (RCTs), either published or unpublished, performed in type 2 diabetic patients with GLP-1 receptor agonists (exenatide and liraglutide), with a duration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Results and conclusions: A total of 21 RCTs (six of which unpublished), enrolling 5429 and 3053 patients (with GLP-1 receptor agonists and active comparator or placebo respectively), was retrieved and included in the analysis.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.