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.