The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes

University of Malaya

Status and phase: Unknown; Phase 4

Conditions: Type2 Diabetes; NAFLD

Treatments: Drug: Empagliflozin

Study type: Interventional

Funder types: Other

Identifiers

NCT02964715

ERF-4

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Interventional arm

Experimental group

Description:

Patients with NAFLD and Type 2 Diabetes prescribed 25mg empagliflozin(JARDIANCE) daily for 6 months

Treatment:

Drug: Empagliflozin