Effects of Ipragliflozin on Excessive Fat in Type 2 Diabetes Patients With Non-alcoholic Fatty Liver Disease Treated With Metformin and Pioglitazone

Type 2 Diabetes With Non-alcoholic Fatty Liver (NAFLD) Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02875821
• Other study ID #: 4-2015-1115
• Status: Completed
• Phase: Phase 4
• First received: August 18, 2016
• Last updated: June 22, 2017
• Start date: April 26, 2016
• Est. completion date: June 7, 2017

Study information

• Verified date: June 2017
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, the investigators investigate beneficial effects of ipragliflozin, newly developted SGLT2 inhibitor, on reduction in visceral fat area and degree of fatty liver in subjects with T2DM when added to metformin and pioglitazone therapy.

Description:

Pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) agonist increase insulin sensitivity in peripheral tissue and liver by protecting non-adipose tissues against excessive lipid overload and by balancing the secretion of adipocytokines.

However, PPARγ is a key transcription factor that induces the differentiation adipocyte maturation and stimulates the induction of enzymes involved in lipogenesis. As a result, the effect of pioglitazone is generally accompanied by weight gain and an increase in amount of subcutaneous fat.

Obesity would coexist with fatty liver disease and both conditions aggravate hyperglycemia in diabetes. According to recent study, up-regulated PPARγ expression in liver was reported in obesity with hepatic steatosis which implies pioglitazone might induce fatty liver disease.

A novel oral antidiabetic drug, sodium glucose cotransporter 2 (SGLT2) inhibitor reduces renal glucose reabsorption and increasing renal glucose excretion thereby promoting energy loss. As a result, it prevents weight gain and fluid retention which might counteract the unfavorable effects of pioglitazone treatment.

No study has been conducted on the additional effect on obesity and fatty liver of ipragliflozin in T2DM patients treated with pioglitazone and metformin.

In this study, the investigators investigate beneficial effects of ipragliflozin, newly developted SGLT2 inhibitor, on reduction in visceral fat area and degree of fatty liver in subjects with T2DM when added to metformin and pioglitazone therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: June 7, 2017
• Est. primary completion date: June 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetic patients

• Diagnosed as NAFLD

• Age of 20~75

• On metformin + pioglitazone treatment with stable dose for at least 8 weeks

• Adequate glycemic control: HbA1c = 9.5%

• Overweight & obese: BMI = 23 kg/m2

• Subject is male, or subject is female who is highly unlikely to conceive

• Understands the study procedure, alternatives, and risks and voluntarily agrees to participate by giving written informed consent

Exclusion Criteria:

• Type 1 diabetes, Secondary diabetes, gestational diabetes

• Heavy alcoholics (men =210 g of alcohol per week, women =140 g of alcohol per week)

• Underlying chronic liver disease (hemochromatosis, liver cell carcinoma, autoimmune liver disease, liver cirrhosis, chronic viral hepatitis [except hepatitis B carrier], Wilson's disease)

• Patients on medication causes hepatic steatosis (e.g.amiodarone, methotrexate, tamoxifen, valproate, corticosteroids, etc)

• Allergy or hypersensitivity to target medication or any of its components

• Renal failure, moderate or severe renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m2), or ongoing dialysis

• Abnormal liver function (AST/ALT > x10 upper normal limit)

• On taking weight loss medication

• History of alcohol or drug abuse in the previous 3 months

• Premenopausal women who are nursing or pregnant

• Human immunodeficiency virus (HIV) or human immunodeficiency virus (AIDS)

• Diabetic ketoacidosis

• Severe infection, severe trauma

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Type 2 Diabetes With Non-alcoholic Fatty Liver (NAFLD)

Intervention

Drug:
• Ipragliflozin
Patients treated with ipragliflozin (50 mg/day) as add on therapy to metformin and pioglitazone dual therapy (triple therapy) for 6 months. During whole periods of study, subjects are educated for nutrition and exercise. (Experimental Group)
• metformin with pioglitazone
Patients maintain metformin and pioglitazone dual therapy for 6 months. During whole periods of study, subjects are educated for nutrition and exercise. (Control group)

Locations

Country	Name	City	State
Korea, Republic of	Yonsei University College of Medicine, Department of internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	changes in visceral fat area	The visceral fat area is measured by dual-energy x-ray absorptiometry (DEXA) at baseline and after 6 months treatment	6 months
Secondary	Changes in subcutaneous fat area	The subcutaneous fat area is measured by dual-energy x-ray absorptiometry (DEXA) and fat computed tomography (CT) at baseline and after 6 months treatment.	6 months after treatment
Secondary	Changes in liver fat	Changes in the degree of fatty liver is measured by fibroscan using controlled attenuation parameter (CAP) score.	6 months after treatment