• Sheldon Russell.
• Barndoc Healthcare Ltd., Churchwood House, Cockfosters Road, London EN4 0DR, UK. sheldon@russellgroup.org.uk
• Int J Clin Pharm. 2013 Apr 1; 35 (2): 159-72.

BackgroundClinical trials comparing incretin-based therapies-glucagon-like peptide-1 receptor agonists (exenatide-twice daily and once weekly-and once-daily liraglutide) and dipeptidyl peptidase-4 inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin)-with placebo and oral antidiabetic drugs show that these therapies effectively control glycaemia, with low risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists are associated with weight loss and reductions in systolic blood pressure, while dipeptidyl peptidase-4 inhibitors are weight-neutral. Based on this, the National Institute for Health and Clinical Excellence recommends using these agents in patients with type 2 diabetes for whom excess weight and/or hypoglycaemia are problematic.Aim Of The ReviewThis review aims to help decision making when selecting and using incretin-based therapies in type 2 diabetes.MethodsA search or MEDLINE and Cochrane clinical trials databases, limited to clinical trials in humans, was performed using the search criteria 'exenatide or liraglutide or vildagliptin or sitagliptin, or saxagliptin or linagliptin'. Abstracts presented at recent American Diabetes Association and European Association for the Study of Diabetes meetings were also searched. Eighteen clinical trials directly comparing incretin-based therapies were identified.ResultsGlucagon-like peptide-1 receptor agonists achieved significantly greater reductions in glycated hemoglobin and weight than dipeptidyl peptidase-4 inhibitors, which have a neutral effect on weight. Between-treatment differences were clinically important. Gastrointestinal side effects were more frequent with glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors. Comparisons between glucagon-like peptide-1 receptor agonists and between dipeptidyl peptidase-4 inhibitors showed that differences within the available agents in the two sub-classes are small. Greater treatment satisfaction was reported with glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors.ConclusionGlucagon-like peptide-1 receptor agonists achieve greater glycated hemoglobin reductions than dipeptidyl peptidase-4 inhibitors, with concomitant weight loss. Probably due to the greater efficacy of glucagon-like peptide-1 receptor agonists, patient satisfaction is greater with these agents compared with dipeptidyl peptidase-4 inhibitors despite injectable versus oral administration and more frequent gastrointestinal side effects with the agonists.

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