Type 2 Diabetes Mellitus
Conditions
Keywords
dapagliflozin, glucose variability
Brief summary
Dapagliflozin improves glycemic variability in subjects with type 2 diabetes mellitus when added to insulin therapy. The primary objective of this study is to assess the effect of dapagliflozin on glucose variability compared to placebo after 12 weeks of treatment in type 2 diabetic patients with inadequate glycemic control on insulin.
Detailed description
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.
Interventions
DRUGDapagliflozin
DRUGPlacebo
Sponsors
AstraZeneca
Severance Hospital
Eulji General Hospital
Kyung Hee University Hospital at Gangdong
The Catholic University of Korea
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Female and male aged 20\ 70 years 2. Type 2 diabetes patients 3. Treatment on basal insulin therapy ≥0.2U/kg/day(±metformin and/or ±sulfonylurea) for at least 12 weeks 4. Inadequate glycemic control ; HbA1c 7.0%\ 10.0% at screening 5. Female of childbearing potential agrees to routinely use of adequate contraception from signing of the informed consent throughout the duration of the study 6. Understands the study procedure, alternatives, and risks and voluntarily agrees to participated by giving written informed consent
Exclusion criteria
1. Type 1 diabetes(Fasting C-peptide ≤ 0.78ng/dL(or 0.26 nM/L)), secondary diabetes, gestational diabetes 2. Insulin therapy modalities containing short or rapid acting insulin (continuous subcutaneous insulin injection, pre-mixed insulin, basal-bolus insulin) 3. History of diabetic ketoacidosis, hyperglycemic hyperosmolar state 4. Estimated glomerular filtration rate \<60 mL/min/1.73 m2 5. History of chronic cystitis or recurrent urinary tract infection 6. Currently on loop diuretics 7. Adrenal insufficiency, pituitary insufficiency 8. Currently on medication known to affect glucose metabolism (e.g. corticosteroids, immunosuppressants) 9. Hemoglobin \<10g/dL in female, \<12g/dL in male 10. Abnormal liver function (AST/ALT \> x3 upper normal limit) 11. On weight loss program or taking weight loss medication 12. NYHA class III, IV congestive heart failure 13. History of acute myocardial infarction, unstable angina, coronary artery bypass graft or stroke within 6 months 14. History of bladder cancer 15. History of malignancy within 5 years 16. Pregnant or lactating women 17. History of excessive alcohol abuse (≥30g/day) 18. Hypersensitivity to SGLT2 inhibitors 19. Patient with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. 20. Subject who the investigator deems inappropriate to participate in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Variability (Coefficient of Variation) | baseline and 12 weeks | CV (Coefficient of Variation) |
| Glycemic Variability (Standard Deviation) | baseline and 12 weeks | SD (Standard Deviation) |
| Glycemic Variability (mean amplitude of glycemic excursion) | baseline and 12 weeks | MAGE(mean amplitude of glycemic excursion) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| glycemic control variables Fasting Plasma Glucose | baseline and each visit(6weeks, 12weeks) | Fasting Plasma Glucose |
| lipid profile Total cholesterol | baseline and each visit(6weeks, 12weeks) | Total cholesterol |
| lipid profile Triglyceride | baseline and each visit(6weeks, 12weeks) | Triglyceride |
| lipid profile HDL-cholesterol | baseline and each visit(6weeks, 12weeks) | HDL-cholesterol |
| lipid profile LDL-cholesterol | baseline and each visit(6weeks, 12weeks) | LDL-cholesterol |
| glycemic control variables 24hr urinary glucose excretion | baseline and 12weeks | 24hr urinary glucose excretion |
| glycemic control variables Changes in insulin dose | baseline and each visit(6weeks, 12weeks) | Changes in insulin dose |
| blood pressure SBP | baseline and each visit(6weeks, 12weeks) | SBP |
| blood pressure DBP | baseline and each visit(6weeks, 12weeks) | DBP |
| glycemic control variables Percentage of patients achieving HbA1c < 6.5% | 12weeks | Percentage of patients achieving HbA1c \< 6.5% |
| glycemic control variables Percentage of patients achieving HbA1c < 7% | 12weeks | Percentage of patients achieving HbA1c \< 7% |
| glycemic control variables HbA1C | baseline and each visit(6weeks, 12weeks) | HbA1C |
Countries
South Korea
Outcome results
None listed