Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy

A Multicenter, Randomized, Double-Blind, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Retagliptin Plus Henagliflozein Added to Metformin Compared to Retagliptin or Henagliflozein in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

2 weeks screening period, 4 weeks run-in period, 24 weeks double-blind treatment period, to evaluate the Safety and Efficacy of Retagliptin Plus Henagliflozein added to Metformin compared to Retagliptin or Henagliflozein in combination with Metformin in Subjects with Type 2 Diabetes who have Inadequate Glycemic Control on Metformin Alone

Inclusion Criteria:

1. Men and women, 18-75 years old (both inclusive) at time of screening visit;
2. Subjects with T2DM with inadequate glycemic control defined as central laboratory HbA1c ≥ 7.5 and ≤ 10.5 % at the screening visit;
3. FPG ≤ 15mmol/L at the screening visit;
4. Stable metformin therapy for at least 8 weeks prior to screening at a dose ≥ 1500 mg per day;
5. 19.0<BMI ≤ 40.0 kg/m2 at the screening visit;

Exclusion Criteria:

1. Moderate or severe impairment of renal function [defined as eGFR<60mL/min/1.73 m2 (estimated by MDRD);
2. Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 160 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg;
3. Cardiovascular diseases within 6 months of the screening visit;
4. ALT and/or AST > 1.5 x ULN and or Total Bilirubin > 1.2 x ULN;
5. Hemoglobin ≤ 100 g/L;
6. CK (creatine kinase) and CK-MB > 3 x ULN;
7. Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma);
8. Administration of any antihyperglycemic therapy, other than metformin,within 2 months prior to screening;