Efficacy and safety of bi‐weekly cofrogliptin treatment replacing daily dipeptidyl peptidase‐4 inhibitors in Chinese patients with type 2 diabetes mellitus: A multicenter, open‐label, randomized controlled phase 2 trial

Aim This study aimed to investigate the efficacy and safety of bi‐weekly cofrogliptin treatment as a replacement for daily dipeptidyl peptidase‐4 inhibitors (DPP‐4is) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This multicenter, open‐label, randomized controlled study assigned participants in a 1:1 ratio to either the daily DPP‐4i group or the 10 mg cofrogliptin group. The DPP‐4i group continued their original daily DPP‐4i regimen for 24 weeks, whereas the cofrogliptin group discontinued the daily DPP‐4i and received the investigational drug orally once every 2 weeks. All participants underwent 14‐day continuous glucose monitoring at weeks 10–12 and 22–24 during the treatment period. The main endpoint was the change in glucose time in range (TIR; 3.9–10.0 mmol/L) from baseline to week 24. Additionally, the Diabetes Treatment Satisfaction Questionnaire scores, adverse events, and hypoglycaemic events were compared between groups. Results The enrolment period was from 31 January 2024 to 20 November 2024. A total of 64 participants were randomized to receive either cofrogliptin ( n = 31) or a daily DPP‐4i ( n = 33). The least squares (LS) mean (standard error) change in TIR from baseline after 24 weeks was 0.037% ± 2.506% in the cofrogliptin group compared to −9.891% ± 2.435% in the daily DPP‐4i group. The LS mean difference was 9.929% (95% confidence interval: 3.064%–16.793%), which was statistically significant ( p = 0.0046). The incidence, classification, and severity of adverse events were similar between the two groups. Conclusion Bi‐weekly cofrogliptin treatment, instead of daily DPP‐4i, could effectively control blood glucose levels in a 24‐week treatment period and their fluctuations and was well tolerated in Chinese patients with T2DM.