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

Diabetes Mellitus, Type 2 Clinical Trial

— DAPHNIS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02577159
• Other study ID #: DAPHNIS
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: July 1, 2015
• Est. completion date: August 31, 2018

Study information

• Verified date: January 2018
• Source: Osaka University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: August 31, 2018
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hyperlipidemias
• Hyperlipoproteinemias
• Insulin Resistance

Intervention

Drug:
• Dapagliflozin
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.

Locations

Country	Name	City	State
Japan	Sousei Hospital	Kadoma	Osaka
Japan	Osaka Central Hospital	Osaka city	Osaka
Japan	Osaka University Hospital	Suita	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Osaka University

Country where clinical trial is conducted

Japan, 

References & Publications (9)

Bolinder J, Ljunggren Ö, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012 Mar;97(3):1020-31. doi: 10.1210/jc.2011-2260. Epub 2012 Jan 11. — View Citation

Hanada H, Mugii S, Okubo M, Maeda I, Kuwayama K, Hidaka Y, Kitazume-Taneike R, Yamashita T, Kawase R, Nakaoka H, Inagaki M, Yuasa-Kawase M, Nakatani K, Tsubakio-Yamamoto K, Masuda D, Ohama T, Matsuyama A, Ishigami M, Nishida M, Komuro I, Yamashita S. Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 and its clinical applications for evaluation of impaired chylomicron remnant metabolism. Clin Chim Acta. 2012 Jan 18;413(1-2):160-5. doi: 10.1016/j.cca.2011.09.013. Epub 2011 Sep 19. — View Citation

Ji L, Ma J, Li H, Mansfield TA, T'joen CL, Iqbal N, Ptaszynska A, List JF. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther. 2014 Jan 1;36(1):84-100.e9. doi: 10.1016/j.clinthera.2013.11.002. Epub 2013 Dec 28. — View Citation

Kaku K, Maegawa H, Tanizawa Y, Kiyosue A, Ide Y, Tokudome T, Hoshino Y, Yang J, Langkilde AM. Dapagliflozin as monotherapy or combination therapy in Japanese patients with type 2 diabetes: an open-label study. Diabetes Ther. 2014 Dec;5(2):415-33. doi: 10.1007/s13300-014-0086-7. Epub 2014 Oct 24. — View Citation

Masuda D, Sakai N, Sugimoto T, Kitazume-Taneike R, Yamashita T, Kawase R, Nakaoka H, Inagaki M, Nakatani K, Yuasa-Kawase M, Tsubakio-Yamamoto K, Ohama T, Nakagawa-Toyama Y, Nishida M, Ishigami M, Masuda Y, Matsuyama A, Komuro I, Yamashita S. Fasting serum apolipoprotein B-48 can be a marker of postprandial hyperlipidemia. J Atheroscler Thromb. 2011;18(12):1062-70. Epub 2011 Sep 24. — View Citation

Masuda D, Sugimoto T, Tsujii K, Inagaki M, Nakatani K, Yuasa-Kawase M, Tsubakio-Yamamoto K, Ohama T, Nishida M, Ishigami M, Kawamoto T, Matsuyama A, Sakai N, Komuro I, Yamashita S. Correlation of fasting serum apolipoprotein B-48 with coronary artery disease prevalence. Eur J Clin Invest. 2012 Sep;42(9):992-9. doi: 10.1111/j.1365-2362.2012.02687.x. Epub 2012 May 15. — View Citation

Mugii S, Hanada H, Okubo M, Masuda D, Takeoka K, Hidaka Y, Ohama T, Matsuyama A, Nakagawa-Toyama Y, Nishida M, Ishigami M, Komuro I, Yamashita S. Thyroid function influences serum apolipoprotein B-48 levels in patients with thyroid disease. J Atheroscler Thromb. 2012;19(10):890-6. Epub 2012 Jul 4. — View Citation

Nakatani K, Sugimoto T, Masuda D, Okano R, Oya T, Monden Y, Yamashita T, Kawase R, Nakaoka H, Inagaki M, Yuasa-Kawase M, Tsubakio-Yamamoto K, Ohama T, Nishida M, Ishigami M, Komuro I, Yamashita S. Serum apolipoprotein B-48 levels are correlated with carotid intima-media thickness in subjects with normal serum triglyceride levels. Atherosclerosis. 2011 Sep;218(1):226-32. doi: 10.1016/j.atherosclerosis.2011.05.009. Epub 2011 May 18. — View Citation

Okubo M, Hanada H, Matsui M, Hidaka Y, Masuda D, Sakata Y, Yamashita S. Serum apolipoprotein B-48 concentration is associated with a reduced estimated glomerular filtration rate and increased proteinuria. J Atheroscler Thromb. 2014;21(9):974-82. Epub 2014 Jun 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.