Effects of Ipragliflozin on Excessive Fat in Type 2 Diabetes Patients With Non-alcoholic Fatty Liver Disease Treated With Metformin and Pioglitazone
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- changes in visceral fat area
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Group IMP
Group IMP (Ipragliflozin with Metformin with Pioglitazone)
干预措施: Ipragliflozin (Drug)
Group MP
Group MP (Metformin with Pioglitazone)
干预措施: metformin with pioglitazone (Drug)
结局指标
主要结局
changes in visceral fat area
时间窗: 6 months
The visceral fat area is measured by dual-energy x-ray absorptiometry (DEXA) at baseline and after 6 months treatment
次要结局
- Changes in subcutaneous fat area(6 months after treatment)
- Changes in liver fat(6 months after treatment)