Disparity of the Efficacy of DPP-4 Inhibitors in Combination with Metformin vs. High Dose Metformin as Initial Treatment between Asian and Caucasian T2DM Patients

Background: To evaluate the efficacy and safety of DPP-4 inhibitors (DPP-4i) in combination with metformin as initial treatment vs. high or low dose of metformin in type 2 diabetes patients. Methods: Studies were identified by search of MEDLINE and EMBASE until Nov. 2017. Inclusion criteria were: T2DM; initial treatment; comparing metformin monotherapy vs.s DPP-4i in combination with metformin therapy; the primary endpoint was the change in HbA1c. Results: A total of 9 studies were included. In Asian drug-naïve T2DM patients, compared with high dose metformin monotherapy(2g/day), high dose metformin initial combine with DPP-4i therapy led to significant decrease in HbA1c (WMD -0.22%), while in Caucasian, combination therapy resulted in -0.53% change. The difference in the reduction of HbA1c between Asian and Caucasian of combination therapy vs. monotherapy was 0.31% with significance in favor of Caucasian population. In terms of fasting plasma glucose (FPG), in Asian patients, combination therapy vs. monotherapy led to -0.40mmol/L change, while in Caucasian, combination therapy vs. monotherapy led to -0.95mmol/L change. The difference in FPG reduction between Asian and Caucasian was 0.55mmol/L with significance in favor of Caucasian patients. The difference in postprandial glucose (PPG) reduction between Asian and Caucasian was 0.94mmol/L in favor of Caucasian. The difference in body weight changes between Asian and Caucasian was 0.50kg with significance body weight gain of Asian patients. Adverse effects were not increased when compared with combination therapy vs. monotherapy. Conclusion: DPP-4i with metformin as initial treatment was superior to metformin given alone in glycemic control of drug-naïve T2DM. The glucose-lowering efficacy of DPP-4i combination therapy was greater in Caucasian patients than in Asian.