1719-P: Efficacy and Safety of Anagliptin Added to Metformin and Empagliflozin 25 mg in Patients with Type 2 Diabetes: A 24-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with 28-Week Open-Label Extension

Introduction and Objective: Type 2 diabetes mellitus (T2DM) patients inadequately controlled with metformin and empagliflozin require additional therapies to improve glycemic control. This study evaluated the efficacy and safety of anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, as add-on therapy to metformin and empagliflozin. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, we enrolled patients with T2DM inadequately controlled (HbA1c 7.0-11.0%) on metformin (≥1000 mg/day) and empagliflozin (25 mg/day). Patients were randomized 1:1 to receive anagliptin (100 mg twice daily) or placebo for 24 weeks, followed by a 28-week open-label extension. The primary endpoint was change in HbA1c from baseline to week 24. Results: Of 200 randomized patients (n=97 anagliptin, n=100 placebo; mean age 58.6 years; baseline HbA1c 7.76%), 197 completed primary analysis. At week 24, HbA1c decreased 0.83% in anagliptin group versus 0.03% in placebo (difference -0.80%; 95% CI -0.95 to -0.64; P<0.0001). More patients achieved HbA1c ≤7.0% (60.8% vs. 18.0%; P<0.0001) and ≤6.5% (25.8% vs. 3.0%; P<0.0001). Fasting plasma glucose decreased 11.1 mg/dL in anagliptin versus increased 5.75 mg/dL in placebo (P<0.0001). HOMA-β improved: +10.45 versus -6.02 (P=0.0003). During open-label extension, placebo-treated patients switching to anagliptin achieved similar HbA1c at week 52 (anagliptin: 7.14% vs. original placebo: 7.17%; P=0.60), while anagliptin group maintained durable efficacy (change from baseline: -0.59%). Adverse events showed no significant difference between groups over 52 weeks (anagliptin 20.2% vs. placebo 29.0%; P=0.15). No severe hypoglycemia or deaths occurred. Conclusion: Anagliptin as add-on therapy to metformin and empagliflozin 25 mg significantly improves glycemic control and β-cell function with a favorable safety profile in T2DM patients inadequately controlled on dual therapy. Disclosure J. Moon: None. S. Park: Employee; Current; JW Pharmaceutical Corporation. J. Won: None. J. Kang: None. K. Han: None. J. Yu: None. C. Park: None.