title: Incretin-based therapies for type 2 diabetes mellitus: a review of direct comparisons of efficacy, safety and patient satisfaction.
abstract: BACKGROUND
  Clinical 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.
  
  
  OBJECTIVE
  This review aims to help decision making when selecting and using incretin-based therapies in type 2 diabetes.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Glucagon-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.
  
  
  CONCLUSIONS
  Glucagon-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.
authors.affiliation: Barndoc Healthcare Ltd., Churchwood House, Cockfosters Road, London EN4 0DR, UK. sheldon@russellgroup.org.uk
authors.forename: Sheldon
authors.initials: S
authors.lastname: Russell
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D054795:Incretins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017060:Patient Satisfaction; D018027:Receptors, Glucagon / Q000819:agonists; D015431:Weight Loss / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D018027:Receptors, Glucagon