SUN-656 - Cofrogliptin Administered Once Every Two Weeks as Add-on Therapy to Low-Dose Metformin and SGLT2 Inhibitors in Patients with Type 2 Diabetes

Introduction and

Objective: Cofrogliptin is a novel ultra-long-acting DPP-4 inhibitor indicated for improving glycemic control in patients with type 2 diabetes mellitus (T2D), either as monotherapy or in combination with other agents. This multicenter, open-label trial aims to assess the safety and efficacy of cofrogliptin as add-on therapy to low-dose metformin and SGLT2i.

Methods: T2D patients failing to achieve adequate glycemic control with SGLT2i plus metformin (HbA₁c≥7.0% after 2 months of treatment) were randomized to the cofrogliptin group (cofrogliptin + metformin + SGLT2i) or metformin titration group (metformin + SGLT2i). The primary endpoint was the change from baseline in HbA₁c levels after 24 weeks of therapy.

Results: This study plans to enroll 80 patients, with 28 patients enrolled to date. In the interim analysis at Week 12, the HbA1c level decreased from 7.7% to 7.4% in all participants (N=6). Both the cofrogliptin group (n=3) and the metformin titration group (n=3) demonstrated a reduction in HbA₁c levels, with decreases from 7.5% to 7.2% and from 7.8% to 7.6%, respectively. Cofrogliptin was well tolerated, with no severe drug-related adverse reactions, serious adverse events, or episodes of hyperglycemia observed in the study.

Conclusion: Preliminary results showed that add-on therapy with cofrogliptin to metformin and SGLT2i demonstrated favorable efficacy in T2D patients who had inadequate glycemic control. Additionally, the triple-drug combination demonstrated a satisfactory safety profile. Further analysis with an expanded sample size over 24 weeks will be updated and presented at the 2026 ENDO Scientific Sessions.
Trial registration: ClinicalTrials.gov, NCT06863532.

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