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

NCT ID: NCT02875821

Last Updated: 2017-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-26
• Study Completion Date: 2017-06-07

Brief 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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group IMP

Group IMP (Ipragliflozin with Metformin with Pioglitazone)

Group Type: EXPERIMENTAL

Ipragliflozin

Intervention Type: DRUG

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)

Group MP

Group MP (Metformin with Pioglitazone)

Group Type: ACTIVE_COMPARATOR

metformin with pioglitazone

Intervention Type: DRUG

Patients maintain metformin and pioglitazone dual therapy for 6 months. During whole periods of study, subjects are educated for nutrition and exercise. (Control group)

Interventions

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)

Intervention Type: DRUG

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)

Intervention Type: DRUG

Other Intervention Names

Suglat®

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yonsei University College of Medicine, Department of internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes Center

Seoul, , South Korea

Countries

South Korea

Other Identifiers

4-2015-1115

Identifier Type: -

Identifier Source: org_study_id