Systematic review and meta-analysis of efficacy and safety of combinational therapy with metformin and dipeptidyl peptidase-4 inhibitors

Combinational therapies are often required in the management of type 2 diabetes mellitus (T2DM). Among the important candidates, dipeptidyl peptidase-4 inhibitors (DPPIs) and metformin combination (DPPI-MET) have shown promising endeavors. In order to examine the efficacy and safety of such a combination therapy in T2DM patients finding inadequate control with metformin, this systematic review and meta-analysis has been conducted. Literature search was made in multiple electronic databases. Inclusion criteria included; RCTs examining the efficacy and safety of DPPI-MET against placebo-MET or MET-only groups of T2DM patients by observing changes in disease endpoints including HbA1c and FPG, and the length of trial be at least 12 weeks. Mean differences based meta-analyses were performed and heterogeneity assessment was carried out. Nineteen studies were selected and included in the meta-analyses. DPPI-MET significantly improved all disease endpoints and the difference could be noticed up to 2 years in the majority of outcome measures. In comparison with PBO-MET, the DPPI-MET combinational therapy resulted in the percent HbA1c changes from baseline with a mean difference [95% CI] of −0.77 [−0.86, −0.69] in 3-month (P < 0.00001), −0.67 [−0.76, −0.59] in 6-month (P < 0.00001), −0.67 [−0.88, −0.47] in 1-year (P < 0.00001) and −0.36 [−0.53, −0.20] in 2-year trials (P < 0.0003). Reduction in body weight and safety profile in the treated and control groups were not different. A combinational therapy with DPPI and metformin significantly improves diabetes clinical indicators and this effect has been observed for up to 2 years herein. Safety and tolerability of DPPI-MET combination have been found well-manageable with a very similar adverse event profile in both treated and control groups.