Efficacy and Safety of the Dual SGLT1 and SGLT2 Inhibitor JP-2266 in Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study.

BACKGROUND

To evaluate the efficacy and safety of JP-2266, a novel dual sodium-glucose co-transporter 1 (SGLT1)/SGLT2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise.

METHODS

In this 12-week, randomized, double-blind, placebo-controlled phase 2 trial, 156 patients with T2DM were randomly assigned (1:1:1) to receive once-daily JP-2266 5 mg (n=51), 10 mg (n=53), or placebo (n=52). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 12 (ClinicalTrials.gov identifier: NCT06144788).

RESULTS

JP-2266 treatment led to significant, placebo-adjusted reductions in HbA1c of -0.94% (95% confidence interval [CI], -1.24 to -0.65; P<0.0001) for the 5 mg dose and -0.97% (95% CI, -1.26 to -0.68; P<0.0001) for the 10 mg dose. Significant reductions were also observed in fasting plasma glucose (-36.22 mg/dL [95% CI, -47.62 to -24.83] with 5 mg and -39.38 mg/dL [95% CI, -50.71 to -28.05] with 10 mg), and postprandial glucose (-62.30 mg/dL [95% CI, -84.97 to -39.64] with 5 mg and -66.89 mg/dL [95% CI, -89.71 to -44.07] with 10 mg) (all P<0.0001). JP-2266 also reduced body weight of -2.0 to -2.1 kg and systolic blood pressure (-3.6 mm Hg with 10 mg). Improvements in insulin resistance and β-cell function were also observed, as assessed by homeostasis model assessment. Adverse event rates were similar to placebo.

CONCLUSION

In patients with T2DM inadequately controlled by lifestyle alone, JP-2266 significantly improved glycemic control, reduced body weight and blood pressure, and was well tolerated over 12 weeks. These findings support further investigation of JP-2266 as a potential therapeutic option for T2DM.