Clinical trial NCT02577159: Dapagliflozin on Hyperlipidemia and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)
Official title: Effects of Dapagliflozin on Hyperlipidemia, Glycemic Control and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: sodium-glucose cotransporter 2 inhibitor
Diabetes Mellitus, Type 2
dyslipidemia
remnants
apolipoprotein B-48
Lead sponsor: Osaka University
Sponsor class: OTHER
First posted: 2015-10-16
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in fasting lipoprotein profiles
timeFrame: at four and eight weeks after the administration of dapagliflozin
Secondary outcomes:
measure: Changes in fasting lipid profiles
timeFrame: at four and eight weeks after the administration of dapagliflozin
measure: Changes in fasting blood glucose and HbA1c
timeFrame: at four and eight weeks after the administration of dapagliflozin
measure: Changes in insulin and adiponectin
timeFrame: at four and eight weeks after the administration of dapagliflozin
measure: Frequency of adverse side effects
timeFrame: at four and eight weeks after the administration of dapagliflozin
measure: Changes in biomarkers for renal and hepatic function
timeFrame: four and eight weeks after the administration of dapagliflozin.
Other outcomes:
Locations:
city: Kadoma
country: Japan
facility: Sousei Hospital
state: Osaka
city: Osaka city
country: Japan
facility: Osaka Central Hospital
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
Study officials:
affiliation: Osaka University Graduate School of Medicine
name: Shizuya Yamashita, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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