Bi-Weekly Cofrogliptin Outperforms Daily DPP-4 Inhibitors in Type 2 Diabetes: Phase 2 Trial
China: A new multicenter phase 2 clinical trial, published in Diabetes, Obesity and Metabolism, suggests that cofrogliptin, administered once every two weeks, could offer an effective and well-tolerated alternative to daily dipeptidyl peptidase-4 inhibitors (DPP-4is) in Chinese patients with type 2 diabetes mellitus (T2DM).
Led by Congqing Pan from the NHC Key Laboratory of Hormones and Development at Tianjin Medical University, the study provides early evidence that a less frequent dosing regimen may maintain glucose control without compromising safety.
The investigation aimed to determine whether bi-weekly cofrogliptin could replace traditional daily DPP-4 inhibitors while sustaining glycemic stability. A total of 64 participants were recruited between January 31 and November 20, 2024, and were randomly assigned to receive either 10 mg cofrogliptin every two weeks (31 patients) or continue their existing daily DPP-4 inhibitor therapy (33 patients). The trial was conducted in an open-label format across multiple centres in China.
Participants underwent continuous glucose monitoring for 14 days during weeks 10–12 and 22–24, giving researchers a detailed picture of glucose patterns. The primary indicator of treatment effectiveness was the change in time in range (TIR)—defined as glucose levels between 3.9 and 10.0 mmol/L—from baseline to week 24.
The analysis led to the following findings:
- The cofrogliptin group showed a minimal change in time in range, with a mean of 0.037% ± 2.506% over 24 weeks.
- Participants on daily DPP-4 inhibitors experienced a drop in TIR of −9.891% ± 2.435% during the same period.
- The least squares mean difference between groups was 9.929%, favouring cofrogliptin, and was statistically significant.
- The findings indicate that cofrogliptin may not only match but also surpass daily DPP-4 inhibitors in maintaining glucose within the recommended range.
- Safety assessments showed similar frequencies and types of adverse events in both groups.
- There was no increase in hypoglycaemia or severe treatment-related complications, supporting the good tolerability of cofrogliptin over the 24-week treatment period.
Despite the encouraging findings, the authors highlight several limitations. The relatively small sample size and the study’s exclusive focus on Chinese patients may restrict broader applicability. The open-label design introduces potential bias, and baseline imbalances—such as differences in sex distribution and diabetes duration—could influence outcomes. Additionally, only four DPP-4 inhibitors were included in the comparison, which may not fully represent the entire class of drugs.
The research team also cautioned that the trial lacked sufficient statistical power to detect rare or long-term adverse effects, highlighting the need for larger, longer-term studies. Moreover, the high baseline TIR of around 84% among participants could limit the ability to generalise the observed glucose improvements to populations with poorer glycemic control.
Despite these constraints, the findings provide a promising foundation. The investigators conclude that bi-weekly cofrogliptin appears capable of maintaining effective glucose control over 24 weeks and is well tolerated, offering a potential alternative for patients seeking less frequent dosing without compromising efficacy.
Reference:
Pan C, Jiang H, Feng Y, Wang S, Zhang J, Wang Z, Zhou Y, Li F, Zhang Z, Li Y, Chen L. 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. Diabetes Obes Metab. 2025 Nov 20. doi: 10.1111/dom.70305. Epub ahead of print. PMID: 41267147.
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