Safety and pharmacokinetic interaction between fotagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin in healthy subjects

Background Dipeptidyl peptidase-4 (DPP-4) inhibitors have significant clinical efficacy for type 2 diabetes mellitus (T2DM). The combination of fotagliptin (FOT) with metformin (MET) is a promising therapeutic approach in MET-resistant patients. The aim of the present study was to evaluate the pharmacokinetic (PK) interaction between FOT and MET in healthy subjects after multiple-dose administration.Methods Eighteen participants received a randomized open-label, three period treatment that included MET 1000 mg alone, co-administration of FOT 24 mg and MET, followed by FOT 24 mg alone. Serial blood samples were collected for PK analysis, which included geometric mean ratios (GMRs) with 90% confidence intervals (CIs), area under the concentration–time curve (AUC), and maximum plasma concentration (Cmax).Results Analysis results showed that for FOT alone or combination therapy, the 90% CIs of the GMR for AUC0-24,ss and Cmax,ss were 102.08% (98.9%, 105.36%) and 110.65% (102.19%, 119.82%), respectively. For MET, they were 113.41% (100.32%, 128.22%) and 97.11% (83.80%, 112.55%) for AUC0-12,ss and Cmax,ss, respectively. FOT or MET monotherapy and the combination therapy with both drugs were well tolerated.Conclusions No PK drug-drug interactions were found in the combination therapy with FOT and MET. Therefore, FOT can be co-administered with MET without dose adjustment.Trial registration The trial is registered at http://www.chinadrugtrials.org.cn/(Registration No. CTR20190221).