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

Phase 4
Conditions
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT02577159
Lead Sponsor
Osaka University
Brief Summary

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

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).

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
DapagliflozinDapagliflozinDiabetic 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.
Primary Outcome Measures
NameTimeMethod
Changes in fasting lipoprotein profilesat four and eight weeks after the administration of dapagliflozin

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

Secondary Outcome Measures
NameTimeMethod
Changes in fasting lipid profilesat four and eight weeks after the administration of dapagliflozin

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

Changes in insulin and adiponectinat four and eight weeks after the administration of dapagliflozin

Changes in other clinical profiles including concentrations of insulin and adiponectin

Frequency of adverse side effectsat four and eight weeks after the administration of dapagliflozin

Frequency of adverse side effects at four and eight weeks after the administration of dapagliflozin

Changes in fasting blood glucose and HbA1cat four and eight weeks after the administration of dapagliflozin

Changes in fasting blood glucose and HbA1c at four and eight weeks after the administration of dapagliflozin

Changes in biomarkers for renal and hepatic functionfour and eight weeks after the administration of dapagliflozin.

Changes in biomarkers for renal and hepatic function at four and eight weeks after the administration of dapagliflozin.

Trial Locations

Locations (3)

Sousei Hospital

🇯🇵

Kadoma, Osaka, Japan

Osaka University Hospital

🇯🇵

Suita, Osaka, Japan

Osaka Central Hospital

🇯🇵

Osaka city, Osaka, Japan

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