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

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

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.

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.

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.