Anti-diabetic Drugs and Fatty Liver Management

Study Overview
=================
Brief Summary
-----------------
Type 2 DM is one of the major risk factors for development of non-alcoholic fatty liver disease. The pooled prevalence of fatty liver among diabetics is 54% (95% CI 45%-64%). Until now there is no well-established treatment for fatty liver disease. Study setting: Randomized controlled trial Study population: Patients with type 2 DM plus Fatty Liver. Arms and Interventions 1. Experimental arms: Group 1: metformin +/- insulin +/- sulfonylurea Group 2: Metformin plus vildagliptin+/- insulin +/- sulfonylurea Group 3: Metformin plus liraglutide+/- insulin+/- sulfonylurea Group 4: Metformin plus empagliflozin +/- insulin +/- sulfonylurea

Detailed Description
-----------------
Rational: Type 2 DM is one of the major risk factors for development of non-alcoholic fatty liver disease. The pooled prevalence of fatty liver among diabetics is 54% (95% CI 45%-64%). Until now there is no well-established treatment for fatty liver disease. Study setting: Randomized controlled trial Study population: Patients with type 2 DM plus Fatty Liver. NAFLD diagnostic criteria: Fatty Liver Index (FLI) 60 or more plus Ultrasound features of fatty liver. - Inclusion criteria Age above 18. 2- HbA1C less than 10. Sample size: Based on the result reported by Armstrong et al, the proportion of patients on standard care who showed resolution of steatosis versus intervention group on liraglutide was 9% vs 39%, using power of 80%, precision of 5%, the minimal required sample size was 24 for each group and we increased it to 30 to compensate for drop-out. So, 120 subjects will be divided into 4 equal groups. Study Design: Interventional (Randomized Clinical Trial) Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking. Study duration: 12 months of follow up Data collection methods and tools Filling the pre-designed structured interview questionnaire from patients that includes: Demographic traits: age, sex, marital status, education, occupation and residency. Habits: smoking, physical exercise, dietary habits, drug use. Social history, focusing on smoking status, occupation, presence of children at home and plans for future pregnancy (as appropriate). Drug history Clinical data about: Present/ past/ family history on thyroid diseases, and autoimmune disease. Comorbidities: hypertension, coronary heart disease, chronic obstructive air way disease (COPD), obesity and others. Medications used: dose, frequency and route of administration. Hospitalization. Body measures: weight, height, body mass index (BMI), waist circumference. Vital signs: pulse, blood pressure, heart rate. The compliance was ascertained through direct questioning at each clinic visits and by inspecting her pill bottles. Patient satisfaction and quality of life will be measured at baseline and at the end of Intervention. Investigations Lab: HCV Ab, HBsAg, HBcAb, ALT, AST, GGT, FBS, HBA1c, PPBS, Fasting insulin, CBC, Cholesterol, LDL, HDL, TGs, uric acid. Calculation of the following score FLI, NAFLD-LFS, FIB-4, NFS. Imaging: ultrasound/FIBROSCAN/ MRI. Adverse effects of the drugs were systematically identified by careful health interview and clinical examinations. T-Bil, AST, ALT, and hematological values were measured for evaluation at every outpatient clinic visit. Follow-up All patients were followed up for twelve months: Dietary follow up. Liver enzymes (ALT, AST and GGT) at least every 3 months and more if clinically indicated Scores follow up: NFS and FIB-4 every 3 months. Fibroscan at end of 1-year follow up. MRI at end of 1-year follow up.

Official Title
-----------------
Efficacy of Vildagliptin, Liraglutide and Empagliflozin in the Management of Fatty Liver Disease Among Patients With Type 2 Diabetes

Conditions
-----------------
Fatty Liver, Nonalcoholic, Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 DM with fatty liver disease. HbA1C less than 10. Exclusion Criteria: Alcohol intake. BMI 40 or more. CKD with e GFR less than 60. chronic liver diseases (chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alfa-1 antitrypsin deficiency) Atherosclerotic cardiovascular disease. Celiac disease. Clinically evident liver cirrhosis. Patients who have ever had medullary thyroid carcinoma (MTC) or who have a family member who has ever had and patients who have multiple endocrine neoplasia syndrome type 2 (MEN 2)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>metformin +/- insulin +/- sulfonylurea | Drug: Metformin<br>* Antidiabetic drugs<br>* Other names: Vildagliptin;|
| Experimental: Group 2<br>Metformin plus vildagliptin +/- insulin +/- sulfonylurea | Drug: Metformin<br>* Antidiabetic drugs<br>* Other names: Vildagliptin;|
| Experimental: Group 3<br>Metformin plus liraglutide +/- insulin+/- sulfonylurea | Drug: Metformin<br>* Antidiabetic drugs<br>* Other names: Vildagliptin;|
| Experimental: Group 4<br>Metformin plus empagliflozin +/- insulin +/- sulfonylurea | Drug: Metformin<br>* Antidiabetic drugs<br>* Other names: Vildagliptin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in steatosis as measured using CAP score (fibroscan) and MRI |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver enzymes |  | 12 months | 
| Changes in fibrosis grade | as measured by transient elastography (Fibroscan) | 12 months |