Effect of Dapagliflozin on Glycemic Variability (DIVE)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Dapagliflozin

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 Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul St.Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dapagliflozin 10mg; a group which treated with dapagliflozin 10mg plus basal insulin therapy	Drug: Dapagliflozin
Placebo Comparator: placebo 10mg; a group which treated with dapagliflozin placebo plus basal insulin therapy	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic Variability (mean amplitude of glycemic excursion)	MAGE(mean amplitude of glycemic excursion)	baseline and 12 weeks
Glycemic Variability (Coefficient of Variation)	CV (Coefficient of Variation)	baseline and 12 weeks
Glycemic Variability (Standard Deviation)	SD (Standard Deviation)	baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glycemic control variables HbA1C	HbA1C	baseline and each visit(6weeks, 12weeks)
glycemic control variables Fasting Plasma Glucose	Fasting Plasma Glucose	baseline and each visit(6weeks, 12weeks)
lipid profile Total cholesterol	Total cholesterol	baseline and each visit(6weeks, 12weeks)
lipid profile Triglyceride	Triglyceride	baseline and each visit(6weeks, 12weeks)
lipid profile HDL-cholesterol	HDL-cholesterol	baseline and each visit(6weeks, 12weeks)
lipid profile LDL-cholesterol	LDL-cholesterol	baseline and each visit(6weeks, 12weeks)
glycemic control variables Percentage of patients achieving HbA1c < 7%	Percentage of patients achieving HbA1c < 7%	12weeks
glycemic control variables Percentage of patients achieving HbA1c < 6.5%	Percentage of patients achieving HbA1c < 6.5%	12weeks
glycemic control variables 24hr urinary glucose excretion	24hr urinary glucose excretion	baseline and 12weeks
glycemic control variables Changes in insulin dose	Changes in insulin dose	baseline and each visit(6weeks, 12weeks)
blood pressure SBP	SBP	baseline and each visit(6weeks, 12weeks)
blood pressure DBP	DBP	baseline and each visit(6weeks, 12weeks)

Collaborators and Investigators

• Sponsor: The Catholic University of Korea
• Collaborators: AstraZeneca; Severance Hospital; Eulji General Hospital; Kyung Hee University Hospital at Gangdong
• Investigators: Principal Investigator: Kun-Ho Yoon, Ph.D., Seoul St. Mary's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: May 26, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimate): June 2, 2015

Study Record Updates

• Last Update Posted (Actual): July 13, 2017
• Last Update Submitted That Met QC Criteria: July 12, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: dapagliflozin; glucose variability
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: ISSDAPA0006