Anti-diabetic Drugs and Fatty Liver Management

Alexandria University

Status: Unknown

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

Treatments: Drug: Metformin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05041673

0304932

Details and patient eligibility

About

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

Full 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

  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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

120 participants in 4 patient groups

Group 1

Active Comparator group

Description:

metformin +/- insulin +/- sulfonylurea

Treatment:

Drug: Metformin

Group 2

Experimental group

Description:

Metformin plus vildagliptin +/- insulin +/- sulfonylurea

Treatment:

Drug: Metformin

Group 3

Experimental group

Description:

Metformin plus liraglutide +/- insulin+/- sulfonylurea

Treatment:

Drug: Metformin

Group 4

Experimental group

Description:

Metformin plus empagliflozin +/- insulin +/- sulfonylurea

Treatment:

Drug: Metformin