Efficacy and safety of incretin based therapies: clinical trial data.
OBJECTIVE
Provide a comprehensive overview of efficacy and safety data on incretin-based agents in the treatment of type 2 diabetes.


METHODS
A PubMed search was conducted for the years 2000-2009, using as keywords the names of glucagon-like peptide-1 (GLP-1) receptor agonists (exenatide and liraglutide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, alogliptin, and saxagliptin). World Diabetes Congress abstracts from 2008 to 2009 were also searched for clinical studies of these agents.


METHODS
The author included randomized controlled trials of incretin therapies that were published in English and enrolled > or =100 participants.


METHODS
Data on the effects of incretins on glycemic control, weight, beta-cell function, blood pressure, lipid levels, safety, and tolerability were extracted and summarized.


RESULTS
A total of 27 randomized controlled studies of incretin therapy were identified and included in the review. GLP-1 receptor agonists and DPP-4 inhibitors were evaluated at different points in the diabetes treatment spectrum, i.e., added to diet and exercise alone (monotherapy) or added to oral antihyperglycemic regimens (combination therapy).


CONCLUSIONS
In addition to decreasing glycemia in type 2 diabetes, incretin therapies may improve other important parameters, including beta-cell function, blood pressure, and lipid levels, with a low risk for hypoglycemia. A comparison of the study data differentiates the clinical profiles of the GLP-1 receptor agonists, which are associated with weight loss, and DPP-4 inhibitors, which are weight neutral, as well as the individual agents within each class.
Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA. whitej@wsu.edu
John
J
White
D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D008055:Lipids; D018027:Receptors, Glucagon; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human; C042807:DPP4 protein, human