Efficacy and safety of DBPR108 (prusogliptin) as an add‐on to metformin therapy in patients with type 2 diabetes: A 24‐week, multi‐centre, randomized, double‐blind, placebo‐controlled, superiority, phase III clinical trial

Abstract

Aim: 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 (T2D) that is inadequately controlled with metformin. Materials and Methods:In this 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2D patients with HbA1c levels ranging from 7.0% to 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 mean (standard error) change from baseline in HbA1c was significantly greater in the DBPR108 group (À0.70% [0.09%]) than in the placebo group (À0.07% [0.11%]) (P < .001), with a treatment difference of À0.63% (95% confidence interval: À0.87%, À0.39%) on the full analysis set. A higher proportion of patients achieved an HbA1c of 6.5% or less (19.7% vs. 8.5%) and an HbA1c of 7.0% or less (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 without causing weight gain. The overall frequency of adverse events was similar between the two groups.Conclusions: DBPR108 as add-on therapy to metformin offered a significant improvement in glycaemic control, was superior to metformin monotherapy (placebo) and was safe and well-tolerated in patients with T2D that is inadequately controlled with metformin.

Prusogliptin (DBPR108) monotherapy in treatment‐naïve patients with type 2 diabetes: A randomized, double‐blind, active and placebo‐controlled, phase 3 study

“…The magnitude of HbA1c reduction relative to the placebo achieved with DBPR108 100 mg in our study was similar to that observed in other studies with DBPR108 20,21 and in other DPP-4…”

“…20 In addition, a 24-week randomized double-blind trial, comparing the safety and efficacy of DBPR108 plus metformin to placebo plus metformin in patients with uncontrolled type 2 diabetes, revealed a significantly greater reduction in HbA1c with DBPR108 100 mg plus metformin compared with placebo plus metformin [À0.70% (0.09%) vs. À0.07% (0.11%)]. 21 Two phase 3 multicentre, randomized, double-blind, placebo-controlled trials (including the present study) and one phase 2 multicentre, randomized, double-blind, placebo-controlled, multiple-dose trial have been successfully completed. Currently, DBPR108 is undergoing a new drug application process with the National Medical Products Administration (NMPA) for the treatment of type 2 diabetes, underscoring its potential as a pivotal therapeutic intervention in this domain.…”

“…The mean HbA1c change from baseline, adjusted for the placebo effect, was recorded at 0.71% 20 . In addition, a 24‐week randomized double‐blind trial, comparing the safety and efficacy of DBPR108 plus metformin to placebo plus metformin in patients with uncontrolled type 2 diabetes, revealed a significantly greater reduction in HbA1c with DBPR108 100 mg plus metformin compared with placebo plus metformin [−0.70% (0.09%) vs. −0.07% (0.11%)] 21 . Two phase 3 multicentre, randomized, double‐blind, placebo‐controlled trials (including the present study) and one phase 2 multicentre, randomized, double‐blind, placebo‐controlled, multiple‐dose trial have been successfully completed.…”

Comparison of the effects of gemigliptin versus glimepiride on cardiac function in patients with type 2 diabetes uncontrolled with metformin: The gemi‐heart study

“…However, it is worth noting that many clinical studies that used DPP-4 inhibitors also adopted a 24-week treatment duration and obtained meaningful results. 14,47,48 Third, echocardiography was used in this study rather than cardiac MRI, which is a more advanced technique that provides more detailed information about the heart muscle and blood flow. However, echocardiography is a more widely available and cost-effective technique that is useful for the evaluation of the structure and function of the heart valves and chambers.…”

“…Second, the 24‐week duration of the study may not have been sufficient to confirm the long‐term cardiovascular safety of the drug. However, it is worth noting that many clinical studies that used DPP‐4 inhibitors also adopted a 24‐week treatment duration and obtained meaningful results 14,47,48 . Third, echocardiography was used in this study rather than cardiac MRI, which is a more advanced technique that provides more detailed information about the heart muscle and blood flow.…”