The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes
- Registration Number
- NCT02964715
- Lead Sponsor
- University of Malaya
- Brief Summary
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.
- Detailed Description
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
1. 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
Study protocol
This is a prospective open-label proof-of-concept study. The investigators plan to recruit 25 Asian patients with biopsy-proven NASH and type 2 diabetes and commence them on empagliflozin 25 mg daily for 6 months. Upon recruitment clinical information will be obtained via an interview and use of a structured questionnaire. Anthropometric measurements will be obtained at baseline and 6 months. A repeat liver biopsy will be performed after 6 months of empagliflozin therapy. MRI and fibroscan of the liver will be conducted at baseline and 6 months. Fasting blood samples will be drawn for glucose, insulin, c-peptide, triglyceride, HDL, LDL, total cholesterol, NEFA(non-esterified fatty acid), HbA1c , liver function test(including albumin, AST, ALT, gamma GT, uric acid, inflammatory markers, FGF(fibroblast growth factor) and other biomarkers at baseline and 6 months.
Patients will be reviewed by a physician at 1 month and 6 months for development of any potential adverse events while on empagliflozin therapy.
Patients will be instructed not to make any significant changes to diet and lifestyle in these 6 months in order to assess to full effect of the intervention with no possible confounding factors.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 25
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Interventional arm Empagliflozin Patients with NAFLD and Type 2 Diabetes prescribed 25mg empagliflozin(JARDIANCE) daily for 6 months
- Primary Outcome Measures
Name Time Method Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System baseline, 6 months liver biopsy
Change in serum FGF 21 baseline and 6 months blood test
- Secondary Outcome Measures
Name Time Method Change in steatosis baseline and 6 months histological
Change in serum uric acid baseline and 6 months serum concentration
Change in lobular inflammation baseline and 6 months histological
Change in serum FGF 19 baseline and 6 months serum concentration
Change in Liver enzymes baseline and 6 months blood test - AST,ALT, gamma GT
Change in ballooning baseline and 6 months histological
Change in metabolic outcome - fasting Tg baseline and 6 months serum concentration
Change in serum IL-6 baseline and 6 months serum concentration
Change in fibroscan and elastography measure of liver stiffness baseline and 6 months imaging
Change in fibrosis baseline and 6 months histological
Change in metabolic outcome -HbA1c baseline and 6 months serum concentration
Change in metabolic outcome - fasting NEFA baseline and 6 months serum concentration
Change in serum adiponectin baseline and 6 months serum concentration
Change in serum TNF alpha baseline and 6 months serum concentration
Change in MRI features of NASH baseline and 6 months serum concentration
Trial Locations
- Locations (1)
University of Malaya
🇲🇾Kuala Lumpur, Wilayah Persekutuan, Malaysia