Predictors of efficacy of GLP-1 agonists and DPP-4 inhibitors: A systematic review.
OBJECTIVE
To identify the determinants of efficacy of glucagon-like peptide-1 receptor agonists (GLP-1A) and dipeptidyl peptidase-4 inhibitors (DPP-4I).


METHODS
MEDLINE and EMBASE were searched between 01/01/2011 and 15/08/2014 for randomized controlled trials of 12-52weeks' duration, which reported the change in glycated hemoglobin (HbA1c) from baseline as the primary end point, and reported data about predictors of efficacy of incretins.


RESULTS
Among 4172 studies found, 77 studies reported data on baseline HbA1c, age, sex, ethnicity, body mass index (BMI), and history of diabetes in relation to change in HbA1c. For DPP-4I, 37 out of 47 studies reported a greater decrease in HbA1c among patients with higher baseline HbA1c. Most DPP-4I studies reported no variation in efficacy in regard to demographic characteristics or BMI. Among 17 studies reporting on GLP-1A, baseline higher HbA1c was reported as predictive of a greater response in 7 out of 9 studies; 13 studies reported data about other factors, without consistent findings.


CONCLUSIONS
Current evidence suggests that higher baseline HbA1c is associated with a greater efficacy of both DPP-4I and GLP-1A therapies in lowering HbA1c. The roles of other potential predictors are less consistent across studies and require further investigation.
Baker IDI Heart and Diabetes Institute, Clinical Diabetes and Epidemiology, Melbourne, Australia; Department of Endocrinology, Diabetology and Metabolic Disease, Avicenne Hospital, SMBH, Paris 13, Bobigny, France; UMR U557 Inserm/U1125 Inra/CNAM/Université Paris 13, Sorbonne Paris Cité, Bobigny, France. Electronic address: helene.bihan@aphp.fr.
Helene
H
Bihan
Baker IDI Heart and Diabetes Institute, Clinical Diabetes and Epidemiology, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia.
Winda L
WL
Ng
Baker IDI Heart and Diabetes Institute, Clinical Diabetes and Epidemiology, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia.
Dianna J
DJ
Magliano
Baker IDI Heart and Diabetes Institute, Clinical Diabetes and Epidemiology, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia.
Jonathan E
JE
Shaw
D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
Determinant factors; Diabetes; Efficacy; Incretin therapy