Clinical trial NCT02459353: Effect of Dapagliflozin on Glycemic Variability
Official title: Effect of Dapagliflozin on Glycemic Variability as an add-on Therapy in Subjects With Type 2 Diabetes Mellitus With in Inadequate Glycemic Control in Insulin: a Multicenter, Placebo-controlled, Double-blind, Randomized Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: dapagliflozin
glucose variability
Lead sponsor: The Catholic University of Korea
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Severance Hospital
name: Eulji General Hospital
name: Kyung Hee University Hospital at Gangdong
First posted: 2015-06-02
Enrollment: 86
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Glycemic Variability (mean amplitude of glycemic excursion)
timeFrame: baseline and 12 weeks
measure: Glycemic Variability (Coefficient of Variation)
timeFrame: baseline and 12 weeks
measure: Glycemic Variability (Standard Deviation)
timeFrame: baseline and 12 weeks
Secondary outcomes:
measure: glycemic control variables HbA1C
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: glycemic control variables Fasting Plasma Glucose
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: lipid profile Total cholesterol
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: lipid profile Triglyceride
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: lipid profile HDL-cholesterol
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: lipid profile LDL-cholesterol
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: glycemic control variables Percentage of patients achieving HbA1c < 7%
timeFrame: 12weeks
measure: glycemic control variables Percentage of patients achieving HbA1c < 6.5%
timeFrame: 12weeks
measure: glycemic control variables 24hr urinary glucose excretion
timeFrame: baseline and 12weeks
measure: glycemic control variables Changes in insulin dose
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: blood pressure SBP
timeFrame: baseline and each visit(6weeks, 12weeks)
measure: blood pressure DBP
timeFrame: baseline and each visit(6weeks, 12weeks)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul St.Mary's Hospital
Study officials:
affiliation: Seoul St. Mary's Hospital
name: Kun-Ho Yoon, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: