Retagliptin Phosphate

To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin.

This multicentre, phase 3 trial consisted of a 16‐week, randomized, double‐blind, placebo‐controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once‐daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add‐on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16.

At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was −0.82% (95% CI, −1.05% to −0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2‐hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported.

Retagliptin 100 mg QD as an add‐on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

Sitagliptin is a dipeptidyl peptidase‐IV inhibitor for the treatment of type 2 diabetes mellitus. In the present study, a sensitive and high‐throughput quantitative method based on the direct analysis in real time tandem mass spectrometry has been developed and validated for the bioanalysis of sitagliptin in rat plasma without chromatographic separation. Sitagliptin and its internal standard retagliptin were detected in positive ion mode by multiple reaction monitoring transitions at m/z 408.2→235.0 and 465.2→260.1, respectively. The method includes a simple solid‐phase extraction sample preparation procedure, through which appropriate and reproducible analytical results within the linear concentration range of 20–2000 ng/mL have been achieved. The intra‐ and interday precisions were <10.6% and the accuracies were ranging from −8.17 to 2.60%. This method has been successfully applied to the pharmacokinetic study of sitagliptin after single intravenous administration in rats. This approach shows considerable promise of direct analysis in real time tandem mass spectrometry method in the high‐throughput bioanalysis.