Predictors of efficacy of GLP-1 agonists and DPP-4 inhibitors: A systematic review

Aims: 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 12-52 weeks' 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. (C) 2016 Published by Elsevier Ireland Ltd.