Effect of Dapagliflozin on Glycemic Variability

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: Dapagliflozin

• Registration Number: NCT02459353
• Lead Sponsor: The Catholic University of Korea

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.

Study Timeline

• Study First Submitted: 2015-05-26
• Study First Submitted QC: 2015-06-01
• Study First Posted: 2015-06-02
• Study Start: 2015-08
• Primary Completion: 2016-12
• Study Completion: 2017-05
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-12
• Last Update Posted: 2017-07-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo 10mg	Placebo	a group which treated with dapagliflozin placebo plus basal insulin therapy
dapagliflozin 10mg	Dapagliflozin	a group which treated with dapagliflozin 10mg plus basal insulin therapy

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
glycemic control variables Fasting Plasma Glucose	baseline and each visit(6weeks, 12weeks)	Fasting Plasma Glucose
lipid profile Triglyceride	baseline and each visit(6weeks, 12weeks)	Triglyceride
lipid profile LDL-cholesterol	baseline and each visit(6weeks, 12weeks)	LDL-cholesterol
glycemic control variables Percentage of patients achieving HbA1c < 6.5%	12weeks	Percentage of patients achieving HbA1c \< 6.5%
glycemic control variables HbA1C	baseline and each visit(6weeks, 12weeks)	HbA1C
lipid profile Total cholesterol	baseline and each visit(6weeks, 12weeks)	Total cholesterol
glycemic control variables 24hr urinary glucose excretion	baseline and 12weeks	24hr urinary glucose excretion
lipid profile HDL-cholesterol	baseline and each visit(6weeks, 12weeks)	HDL-cholesterol
glycemic control variables Percentage of patients achieving HbA1c < 7%	12weeks	Percentage of patients achieving HbA1c \< 7%
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

Trial Locations

Locations (1)

Seoul St.Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of