The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes
试验速览
- 阶段
- 4 期
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System
研究概览
简要总结
Non-Alcoholic Fatty Liver Disease( NAFLD) is common in patients with type 2 diabetes. Empagliflozin, an FDA-approved oral medication used to treat type 2 diabetes, has been shown to reduce production and deposition of fat in the liver in animal experiments. There is little published evidence that this is so in Asian patients with type 2 diabetes. The investigators designed this pilot study to determine if use of empagliflozin for 6 months in patients with type 2 diabetes can improve scan, blood marker and biopsy features of NAFLD.
详细描述
Empagliflozin, an FDA-approved SGLT2 (Sodium glucose transporter 2) inhibitor used to treat type 2 diabetes, has been shown to reduce hepatic de novo lipogenesis and hepatic steatosis in animal models. There is little published evidence that this is so in Asian patients with type 2 diabetes. The investigators designed this open label proof of concept trial to determine if use of empagliflozin for 6 months in patients with type 2 diabetes can improve biomarkers and histological features of biopsy proven NAFLD.
Hypotheses
- 6 months of empagliflozin will result in improved histology on liver biopsy in type 2 dm patients with NAFLD
2.6 months of empagliflozin will result in changes in liver enzymes, adipocytokines and FGF levels in type 2 dm patients with NAFLD
3.6 months of empagliflozin will result in improved liver stiffness measurement in type 2 dm patients with NAFLD
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
open label
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •biopsy proven NASH
- •Type 2 DM
- •HbA1c :>6.5%
- •BMI < 45kg/m2
- •Any anti-diabetic agent except SGLT2 inhibitors, TZDs(thiazolidinediones), DPP4(Dipeptidyl peptidase4) inhibitors and GLP1 RAs(Glucagon-like Peptide 1-Receptor Agonists)
排除标准
- •eGFR <45 ml/min
- •structural and functional urogenital abnormalities, that predispose for urogenital infections
- •Investigational product use in the last 6 months
- •SGLT2 inhibitor, TZD, DPP4 inhibitor and GLP1 RA use within the past 6 months
- •DKA(Diabetic Ketoacidosis) or HHS(Hyperosmoloar Hyperglycaemic Syndrome) within the last 6 months
- •Pregnancy
- •Presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties).
- •Liver cirrhosis
- •Type 1 diabetes
- •Severe uncorrected insulin insufficiency
- •Significant alcohol intake
- •HIV infection
- •Use of Traditional Chinese Medication or alternative therapies
- •Coexisting causes of chronic liver disease - chronic viral hepatitis(B & C), autoimmune liver disease, hemochromatosis, Wilson's etc.
- •Use of medications associated with steatosis eg. Methotrexate, anticonvulsants, antiretroviral therapy etc.
- •h/o stroke
- •Steroid therapy
- •Endogenous Cushing's
- •Familial hypertriglyceridemia
研究组 & 干预措施
Interventional arm
Patients with NAFLD and Type 2 Diabetes prescribed 25mg empagliflozin(JARDIANCE) daily for 6 months
干预措施: Empagliflozin (Drug)
结局指标
主要结局
Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System
时间窗: baseline, 6 months
liver biopsy
Change in serum FGF 21
时间窗: baseline and 6 months
blood test
次要结局
- Change in lobular inflammation(baseline and 6 months)
- Change in MRI features of NASH(baseline and 6 months)
- Change in steatosis(baseline and 6 months)
- Change in serum FGF 19(baseline and 6 months)
- Change in serum uric acid(baseline and 6 months)
- Change in Liver enzymes(baseline and 6 months)
- Change in ballooning(baseline and 6 months)
- Change in metabolic outcome - fasting Tg(baseline and 6 months)
- Change in serum IL-6(baseline and 6 months)
- Change in fibroscan and elastography measure of liver stiffness(baseline and 6 months)
- Change in fibrosis(baseline and 6 months)
- Change in metabolic outcome -HbA1c(baseline and 6 months)
- Change in metabolic outcome - fasting NEFA(baseline and 6 months)
- Change in serum adiponectin(baseline and 6 months)
- Change in serum TNF alpha(baseline and 6 months)
研究者
Shireene Vethakkan
Associate Professor Dr.
University of Malaya