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.

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.

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