Xu_2022_Diabetes.Obes.Metab__

AIMS: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl-peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with metformin. MATERIALS AND METHODS: In this 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2DM patients with glycated hemoglobin A1c (HbA1c) levels ranging from 7.0-9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108+metformin and placebo+metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS: At week 24, the least-square (LS) mean (standard error [SE]) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than that in the placebo group (-0.07% [0.11%]) (P-value <0.001), with a treatment difference of -0.63% (95% confidence interval [CI]: -0.87, -0.39) on full analysis set. A higher proportion of patients achieved an HbA1c >=6.5% (19.7% vs. 8.5%) and HbA1c >=7.0% (50.0% vs. 21.1%) at week 24 in the DBPR108+metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose (2-h PPG) without causing weight gain. The overall frequency of adverse events (AEs) was similar between the two groups. CONCLUSIONS: DBPR108 as add-on therapy to metformin offered a significant improvement in glycemic control, was superior to metformin monotherapy (placebo), and was safe and well-tolerated in T2DM patients that is inadequately controlled with metformin. This article is protected by copyright. All rights reserved.