Anti-diabetic Drugs and Fatty Liver Management

Not Applicable

• Conditions: Fatty Liver, Nonalcoholic; Diabetes Mellitus, Type 2
• Interventions: Drug: Metformin

• Registration Number: NCT05041673
• Lead Sponsor: Alexandria University

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

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.

Study Timeline

• Study Start: 2021-02-23
• Study First Submitted: 2021-09-02
• Study First Submitted QC: 2021-09-10
• Study First Posted: 2021-09-13
• Primary Completion: 2021-09-30
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-14
• Last Update Posted: 2022-01-18
• Study Completion: 2022-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Metformin	metformin +/- insulin +/- sulfonylurea
Group 2	Metformin	Metformin plus vildagliptin +/- insulin +/- sulfonylurea
Group 3	Metformin	Metformin plus liraglutide +/- insulin+/- sulfonylurea
Group 4	Metformin	Metformin plus empagliflozin +/- insulin +/- sulfonylurea

Primary Outcome Measures

Name	Time	Method
Change in steatosis as measured using CAP score (fibroscan) and MRI	12 months

Secondary Outcome Measures

Name	Time	Method
Changes in fibrosis grade	12 months	as measured by transient elastography (Fibroscan)
Change in liver enzymes	12 months

Trial Locations

Locations (1)

Alexandria University.; 🇪🇬 Alexandria, Egypt