Safety, Pharmacokinetics, and Pharmacodynamics of a Dipeptidyl Peptidase‐4 Inhibitor: A Randomized, Double‐Blinded, Placebo‐Controlled Daily Administration of Fotagliptin Benzoate for 14 Days for Type 2 Diabetes Mellitus

• Published in: Clinical pharmacology in drug development 2021-06, Vol.10 (6), p.660-668
• Main Authors: Wu, Min, Li, Qian‐Qian, Zhang, Hong, Zhu, Xiao‐Xue, Li, Xiao‐Jiao, Li, Ying, Sun, Hai‐Gang, Ding, Yan‐Hua
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Area Under Curve; Blood Glucose - drug effects; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - pharmacokinetics; Double-Blind Method; Female; fotagliptin benzoate, pharmacodynamics, pharmacokinetics, safety; Glucagon-Like Peptide 1 - blood; Glycated Hemoglobin A - metabolism; Humans; Male; Middle Aged; Pharmacodynamics; Pharmacokinetics; Piperidines - administration & dosage; Piperidines - adverse effects; Piperidines - pharmacokinetics; Triazines - administration & dosage; Triazines - adverse effects; Triazines - pharmacokinetics; type 2 diabetes mellitus
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.895

This study investigated the pharmacokinetics, pharmacodynamics, and safety of fotagliptin benzoate (fotagliptin), a dipeptidyl peptidase‐4 (DPP‐4) inhibitor, in Chinese patients with type 2 diabetes mellitus (T2DM). In a randomized, double‐blinded, placebo‐controlled study, 10 and 4 patients with T2DM were randomized and received, respectively, once‐daily oral fotagliptin (24 mg) or placebo, for 14 days. The pharmacokinetics and pharmacodynamics were assessed throughout the study, including monitoring DPP‐4, glucagon‐like peptide‐1 (GLP‐1), glycosylated hemoglobin, and fasting blood glucose. Fotagliptin was rapidly absorbed, and the median time to maximum concentration value was ∼1.5 hours. Plasma fotagliptin levels were stable after 14 days of once‐daily dosage. The accumulation ratios for the area under the plasma concentration–time curve of fotagliptin, M1, and M2‐1, were 1.19 ± 0.10, 1.59 ± 0.27, and 1.39 ± 0.26, respectively. The durations for DPP‐4 inhibition >80% in the fotagliptin group on days 1 and 14 were 23.5 and 24.0 hours, respectively. The concentrations of GLP‐1 were higher on days 1 and 14 than at the baseline. No serious complications occurred. Fotagliptin showed favorable pharmacokinetics and pharmacodynamics and was well tolerated. Treatment with fotagliptin can achieve high DPP‐4 inhibition and increase plasma GLP‐1. A once‐per‐day dosing regimen may be recommended as clinically efficacious.