Effect of Dapagliflozin on Glycemic Variability

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dapagliflozin, glucose variability