Baseline glycemic parameters predict the hemoglobin A_1c response to DPP-4 inhibitors

Ability to predict which patients might benefit more of therapy might facilitate personalization of treatment. The aim of this study was to obtain information about clinical characteristics which might predict the HbA1c response to DPP-4 inhibitors. We conducted an electronic search without restriction for randomized controlled trials (RCTs) involving DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin, and alogliptin). RCTs were included if they lasted at least 12 weeks, reported the effect of DPP-4 inhibitors on HbA1c level, and the number of patients in any arm was >30. We did a meta-regression analysis. Seventy-eight articles were eligible, with 79 arms and 20,503 patients. For all arms, the decrease of HbA1c was −0.74 % (95 % CI −0.80 to −0.67 %), with considerable heterogeneity (I ² = 97 %, P < 0.0001): the greatest HbA1c decrease was seen at 52 weeks (8 arms, 3,338 patients, −0.88 %, 95 % CI −1.10 to −0.66 %). In univariate meta-regression analysis, baseline HbA1c explained 22 % of variance of the HbA1c response to treatment, while fasting glucose and type of DPP-4 inhibitor explained an additional 19 and 12 %, respectively; age, duration of treatment, previous therapy, and type of statistical analysis of RCTs were without influence. In the multivariate meta-regression model, baseline HbA1c, fasting glucose, and type of DPP-4 inhibitor explained 61 % of total variance. The HbA1c response to DPP-4 inhibitors can be modulated mainly by baseline HbA1c and fasting glucose levels: a greater absolute reduction of baseline HbA1c is seen in patients with higher baseline HbA1c and lower fasting glucose level.