Dapagliflozin on Hyperlipidemia and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)

Study Overview
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Brief Summary
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The investigators will investigate whether dapagliflozin (FORXIGA) might improve lipoprotein metabolism as well as hyperglycemia in Japanese patients with type II diabetes mellitus whose HbA1c levels are less than 7.0% (from 20 to 65 years of age). The investigators will examine changes of fasting lipoprotein profile including TG, TC, HDL-C, apoB-48 and RemL-C before and after the 8 weeks administration of dapagliflozin.

Detailed Description
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In this study, the investigators will investigate whether dapagliflozin (FORXIGA) might improve lipoprotein metabolism as well as hyperglycemia in Japanese patients with type II diabetes mellitus. Primary Objective is to examine changes of fasting lipoprotein profile by the administration of dapagliflozin; Concentrations of apoB-48 and RemL-C. Secondary Objectives are; to examine changes of fasting glucose and HbA1c (NGSP) level by the administration of dapagliflozin, to examine changes of fasting lipid profile by the administration of dapagliflozin; Concentrations of TG, TC, HDL-C and LDL-C, to examine changes of fractions of free fatty acids, protein mass of LPL, and lipoprotein profile assessed by the HPLC by the administration of dapagliflozin, to examine changes of biomarkers for renal and hepatic function by the administration of dapagliflozin, and to examine the frequency of adverse effects by the administration of dapagliflozin. This study is open-label study and contains patients who are diabetes mellitus of from 20 to 65 years of age and their Patients who have not achieve the clinical target of the glycemic control (less than 7.0% in HbA1c).

Official Title
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Effects of Dapagliflozin on Hyperlipidemia, Glycemic Control and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects with type 2 diabetes mellitus of from 20 to 65 years of age. Patients who have not achieve the clinical target of the glycemic control (less than 7.0% in HbA1c). Patients who received the diet therapy, the exercise therapy or the following anti-diabetic drugs in addition to the diet and/or exercise therapy (up to two drugs) with dosage stable for 8 weeks prior to entry. Sulfonylurea (Glymepiride 2mg/day or less, Glibenclamide 1.25mg/day or less, Gliclazide 40mg/day or less) Thiazolidine (Actos) Biguanide (Metformin, Buformin) alpha-glucosidase inhibitor (Voglibose, Miglitol, Acarbose) DPP4 inhibitors (Sitagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Saxagliptin) Informed consent to participate in the study prior to any study procedures. Exclusion Criteria: Type 1 diabetes mellitus Moderate or severe renal dysfunction (eGFR<45 ml/min/1.73m2 or hemodialysis) Severe hepatic insufficiency (AST and/or ALT >3x upper limit of normal) Adrenal insufficiency or pituitary gland dysfunction Malnourishment, starvation, irregular dietary intake, poor dietary intake, debilitating condition or a severe muscle movement Volume depleted patients; concomitant medication such as loop diuretics. Excessive alcohol intake (>60g daily) SGLT2 inhibitors such as dapagliflozin are already administered Contraindication with dapagliflozin Start a new medication of statins, fibrates, ezetimibe or probucol within a month Females who are likely to be pregnant, during pregnancy or lactating Participants in other clinical trials Inability to communicate and comply with all study requirements.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Diabetic patients who met the inclusion/exclusion criteria. Dapagliflozin is orally administered for 8 weeks in the dose of 5mg per day if there is no serious event included in termination criteria. If the effect for improving diabetes is insufficient, it is allowed to raise its dose up to 10mg/day. | Drug: Dapagliflozin<br>* Dapagliflozin is orally administered for 8 weeks in the dose of 5mg per day by adding the conventional treatment if there is no serious event included in termination criteria. If the effect for improving diabetes is insufficient, it is allowed to raise its dose up to 10mg/day.<br>* Other names: conventional treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fasting lipoprotein profiles | Changes in fasting lipoprotein profiles including concentrations of apoA-1, apoA-2, apoB, apoB-48, apoC-2, apoC-3, apoE, RemL-C, free-fatty acids profile, LPL protein mass and lipoprotein profile assessed by the HPLC at four and eight weeks after the administration of dapagliflozin | at four and eight weeks after the administration of dapagliflozin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fasting lipid profiles | Changes in fasting lipid profiles including concentrations of triglyceride(TG), total cholesterol(TC), HDL-cholesterol (HDL-C) and LDL-C at four and eight weeks after the administration of dapagliflozin | at four and eight weeks after the administration of dapagliflozin | 
| Changes in fasting blood glucose and HbA1c | Changes in fasting blood glucose and HbA1c at four and eight weeks after the administration of dapagliflozin | at four and eight weeks after the administration of dapagliflozin | 
| Changes in insulin and adiponectin | Changes in other clinical profiles including concentrations of insulin and adiponectin | at four and eight weeks after the administration of dapagliflozin | 
| Frequency of adverse side effects | Frequency of adverse side effects at four and eight weeks after the administration of dapagliflozin | at four and eight weeks after the administration of dapagliflozin | 
| Changes in biomarkers for renal and hepatic function | Changes in biomarkers for renal and hepatic function at four and eight weeks after the administration of dapagliflozin. | four and eight weeks after the administration of dapagliflozin. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sodium-glucose cotransporter 2 inhibitor, Diabetes Mellitus, Type 2, dyslipidemia, remnants, apolipoprotein B-48