Placebo-subtracted reductions from baseline in HbA1c were 0.34% and 0.52%, from a baseline HbA1c of ∼ 8.4%, and dutogliptin also significantly reduced FPG. 216 Patients were randomized to receive oral doses of dutogliptin 200 mg and 400 mg once daily. 215ĭutogliptin was evaluated in a 12-week phase II study in T2DM patients not optimally controlled with metformin and/or thiazolidinediones. Near-maximal DPP-4 inhibition for 24 h was observed at the 300 and 500 mg doses, and the EC 50 and EC 90 values for DPP-4 inhibition by PHX1149 in vivo were ∼ 10 and ∼ 100 ng mL − 1, respectively. Dose-dependent maximal inhibition of DPP-4 ranging from 64% to 92% was observed 2–4 h post dose. 214 In a single-dose study of PHX1149 at 50, 100, 200, 300, or 500 mg in healthy male subjects after an overnight fast, mean drug AUC increased in a dose-proportional manner with a median T max of 2–4 h. 214, 215 PK and PD studies indicate that PHX1149 inhibits DPP-4 enzymatic activity across preclinical species in a time- and dose-dependent manner.

Dutogliptin is a highly water-soluble (> 2 g mL − 1) DPP-4 inhibitor with 15- to 319-fold selectivity over other members of the DPP family and a DPP-4 IC 50 of 25 nM. SinhaRoy, in Comprehensive Medicinal Chemistry III, 2017 7.14.5.2.1 Dutogliptin (PHX1149, Phenomix Corp)ĭutogliptin (PHX1149) 127 is a boronic acid-based DPP-4 inhibitor.

Half life 2 abh