Effects of Berberine Ursodeoxycholate (HTD1801) Versus Dapagliflozin in Patients With Type 2 Diabetes Inadequately Controlled With Metformin

A Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled (Dapagliflozin), Parallel Group Efficacy and Safety Study of HTD1801 in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone

The goal of this clinical study is to evaluate the efficacy and safety of berberine ursodeoxycholate (HTD1801) compared to dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone.

This Phase 3 randomized, double-blind, active-controlled, parallel-group study will evaluate the efficacy and safety of HTD1801 compared to dapagliflozin after 24 weeks of treatment. All patients will remain on a stable dose of metformin throughout the study.

To ensure stabilization of glycemic control, eligible patients will first participate in a 4-week single-blind run-in period where investigators will provide guidance on lifestyle modification, concomitant medications, and procedures for self-monitoring of blood glucose. Following this period, patient eligibility will be reassessed. Eligible patients will then be randomized 1:1 to receive HTD1801 1000 mg BID or dapagliflozin 10 mg QD.

Inclusion Criteria:

• Have been diagnosed with type 2 diabetes
• Have received a stable dose of metformin monotherapy for at least 8 weeks prior to screening
• If used any glucose-lowering drugs other than metformin within the 8 weeks prior to screening such use was ≤7 days and was discontinued at least 4 weeks prior to screening
• Have HbA1c ≥7.5% to ≤11.0% (screening) and HbA1c ≥7.0% to ≤10.5% (pre-randomization)
• Have fasting plasma glucose ≤13.9 mmol/L (screening and pre-randomization)
• Have a body mass index ≥19.0 kg/m^2 and ≤35.0 kg/m^2

Exclusion Criteria:

• Have type 1 diabetes
• Have had any acute diabetic complications within 12 months prior to screening
• Have had any Grade 3 hypoglycemic event within 12 months prior to screening
• Have had proliferative retinopathy or macular degeneration, severe diabetic neuropathy, or diabetic foot
• Have been taking any weight loss medication or dietary supplement, have participated in a weight loss program, or have adhered to a special diet within 12 weeks prior to screening
• Have used insulin or an insulin analogue for more than 14 days within 12 months prior to screening
• Have used any hypoglycemic drug other than metformin during the 4-week run-in period prior to randomization
• Have had weight gain or loss ≥5% during the 4-week run-in period prior to randomization
• Have a history of refractory or recurrent urinary tract infections or genital infections