Prusogliptin

This study aimed to assess the efficacy and safety of prusogliptin (DBPR108), a novel and highly selective dipeptidyl peptidase‐4 inhibitor, in individuals with type 2 diabetes who had not been using glucose‐lowering agents regularly for the 8 weeks before the screening period.

In this multicentre, randomized, double‐blind, phase 3 study, adult patients with type 2 diabetes were randomly assigned to receive either DBPR108 100 mg, sitagliptin 100 mg, or placebo once daily during the initial 24‐week double‐blind treatment period, followed by a 28‐week open‐label extension period during which all patients received DBPR108 100 mg once daily. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) levels from baseline to week 24.

In total, 766 patients were enrolled and received DBPR108 100 mg (n = 462), sitagliptin 100 mg (n = 152), or placebo (n = 152). The mean age of all patients was 54.3 ± 10.5 years, with 58% being men. The median duration of type 2 diabetes was 0.38 (0.02, 2.65) years, and the mean HbA1c (SD) at baseline was 7.94% (0.62), 7.88% (0.61) and 7.83% (0.59) for DBPR108, sitagliptin and placebo groups, respectively. At week 24, the least square mean (SE) changes from baseline in HbA1c were −0.63% (0.04%) for DBPR108, −0.60% (0.07%) for sitagliptin and −0.02% (0.07%) for placebo. The mean treatment difference between DBPR108 and placebo was −0.61% (95% CI –0.77% to −0.44%), and between DBPR108 and sitagliptin was −0.03% (95% CI –0.19% to 0.13%). These results indicate that DBPR108 was superior to placebo and non‐inferior to sitagliptin. DBPR108 also significantly reduced fasting and postprandial plasma glucose levels and had little effect on body weight. The mean (SD) changes in HbA1c from baseline to week 52 were −0.50% (0.97%) for the DBPR108 group, −0.46% (0.96%) for the sitagliptin group and −0.41% (0.95%) for the placebo group. The incidence of adverse events was comparable across all three groups.

DBPR108 showed superiority to placebo and non‐inferiority to sitagliptin in terms of glycaemic control over the initial 24 weeks in treatment‐naïve patients with type 2 diabetes. Furthermore, its efficacy was sustained for up to 52 weeks.

Prusogliptin is a potent and selective DPP-4 inhibitor. In different animal models, Prusogliptin showed potential efficacy in the treatment of type 2 diabetes. However, the knowledge of its pharmacokinetics and safety in patients with liver dysfunction is limited.

The present study evaluated the pharmacokinetics and safety of Prusogliptin in subjects with mild or moderate hepatic impairment compared with healthy subjects.

According to the liver function of the subjects, we divided them into a mild liver dysfunction group, a moderate liver dysfunction group and a normal liver function group. All subjects in three groups received a single oral dose of Prusogliptin 100-mg tablets. Pharmacokinetics and safety index collection was carried out before and after taking the drug. Plasma pharmacokinetics of Prusogliptin were evaluated, and geometric least- -squares mean (GLSM) and associated 90% confidence intervals for insufficient groups versus the control group were calculated for plasma exposures.

After a single oral administration of 100 mg of Prusogliptin tablets, the exposure level of Prusogliptin in subjects with mild liver dysfunction was slightly higher than that in healthy subjects. The exposure level of Prusogliptin was significantly increased in subjects with moderate liver dysfunction. There were no adverse events in this study.

The exposure level of Prusogliptin in subjects with liver dysfunction was higher than that in healthy subjects. No participant was observed of adverse events. Prusogliptin tablets were safe and well tolerated in Chinese subjects with mild to moderate liver dysfunction and normal liver function.