Effect of Dapagliflozin on Glycemic Variability

This study is a multicenter, randomized, double-blind, placebo-controlled phase 4 study to evaluate whether treatment with dapagliflozin add-on to insulin reduces glucose variability in type 2 Diabetes Mellitus. The study will recruit type 2 Diabetes Mellitus patients with inadequate glucose control on insulin treatment with or without metformin or sulphonylurea. It is estimated that 90 type 2 diabetic patients will be enrolled. After randomization, a total 12 week treatment of dapagliflozin or matching placebo will be administered. Before and after treatment, tests for efficacy and safety outcomes will be performed.

Inclusion criteria

• Female and male aged 20~70 years
• Type 2 diabetes patients
• Treatment on basal insulin therapy ≥0.2U/kg/day(±metformin and/or ±sulfonylurea) for at least 12 weeks
• Inadequate glycemic control ; HbA1c 7.0%~10.0% at screening
• Female of childbearing potential agrees to routinely use of adequate contraception from signing of the informed consent throughout the duration of the study
• Understands the study procedure, alternatives, and risks and voluntarily agrees to participated by giving written informed consent

Exclusion criteria

• Type 1 diabetes(Fasting C-peptide ≤ 0.78ng/dL(or 0.26 nM/L)), secondary diabetes, gestational diabetes
• Insulin therapy modalities containing short or rapid acting insulin (continuous subcutaneous insulin injection, pre-mixed insulin, basal-bolus insulin)
• History of diabetic ketoacidosis, hyperglycemic hyperosmolar state
• Estimated glomerular filtration rate <60 mL/min/1.73 m2
• History of chronic cystitis or recurrent urinary tract infection
• Currently on loop diuretics
• Adrenal insufficiency, pituitary insufficiency
• Currently on medication known to affect glucose metabolism (e.g. corticosteroids, immunosuppressants)
• Hemoglobin <10g/dL in female, <12g/dL in male
• Abnormal liver function (AST/ALT > x3 upper normal limit)
• On weight loss program or taking weight loss medication
• NYHA class III, IV congestive heart failure
• History of acute myocardial infarction, unstable angina, coronary artery bypass graft or stroke within 6 months
• History of bladder cancer
• History of malignancy within 5 years
• Pregnant or lactating women
• History of excessive alcohol abuse (≥30g/day)
• Hypersensitivity to SGLT2 inhibitors
• Patient with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• Subject who the investigator deems inappropriate to participate in this study