anti-diabetic drugs and fatty liver management

Conditions: Fatty Liver, Nonalcoholic; Diabetes Mellitus, Type 2

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

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 1. 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 1. 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 2. 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. 3. 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.

Eligibility criteria:
inclusion criteria: * type 2 dm with fatty liver disease. * hba1c less than 10. exclusion criteria: 1. alcohol intake. 2. bmi 40 or more. 3. ckd with e gfr less than 60. 4. chronic liver diseases (chronic viral hepatitis, autoimmune hepatitis, wilson's disease, hemochromatosis, alfa-1 antitrypsin deficiency) 5. atherosclerotic cardiovascular disease. 6. celiac disease. 7. clinically evident liver cirrhosis. 8. 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)