834-P: Efficacy and Tolerability of Initial Triple Combination Therapy with Metformin, Dapagliflozin, and Saxagliptin Compared with Conventional Stepwise Add-on Therapy in Drug-Naïve Patients with Type 2 Diabetes—A Randomized, 104-Week, Open-Label, Active-Controlled Trial

Background: Early combination therapy is recommended in type 2 diabetes (T2D) patients with inadequately controlled hyperglycemia to avoid treatment failure and clinical inertia. This study aimed to evaluate the efficacy and tolerability of an initial triple combination with metformin, dapagliflozin and saxagliptin compared with conventional stepwise add-on therapy in drug-naïve patients with T2D.

Methods: This multicenter, randomized, 104-week, open-label trial was conducted at 9 medical centers in South Korea. Eligible patients were aged ≥18 years, inadequately controlled (HbA1c ≥ 8.0% to <11.0%), drug-naïve patients with recent-onset T2D. Eligible participants were randomly assigned (1:1) to triple combination therapy (TCT, 1000mg of metformin, 10mg of dapagliflozin and 5mg of saxagliptin once daily) or conventional stepwise therapy (CST) group. CST was started with metformin followed by glimepiride, and sitagliptin sequentially. The primary outcome was the proportion of patients who achieved HbA1c <6.5% without hypoglycemia, weight gain ≥5% and discontinuation due to adverse events at week 104.

Results: A total of 105 eligible participants were randomly assigned to either TCT or CST groups. 89.6% of participants completed the study and treatment. The primary outcome was achieved in 42.5% of the TCT group and 17.5% of the CST group (p=0.015). The proportion of achieving HbA1c <6.5% at week 104 was 50.0% of the TCT group and 45.0% of the CST group. Hypoglycemia, weight gain >5%, or discontinuation due to adverse events occurred in 14.9% of the TCT group, and 59.2% of the CST group.

Conclusion: Initial combination therapy with metformin, dapagliflozin and saxagliptin effectively lowered HbA1c with higher tolerability compared with conventional stepwise treatment in recent-onset T2D.