Anti-diabetic Drugs and Fatty Liver Management

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 2; Fatty Liver, Nonalcoholic
• Intervention / Treatment: Drug: Metformin

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21131
    • Alexandria University.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group 1; metformin +/- insulin +/- sulfonylurea	Drug: Metformin; Antidiabetic drugs; Other Names: Liraglutide; empagliflozin; Vildagliptin
EXPERIMENTAL: Group 2; Metformin plus vildagliptin +/- insulin +/- sulfonylurea	Drug: Metformin; Antidiabetic drugs; Other Names: Liraglutide; empagliflozin; Vildagliptin
EXPERIMENTAL: Group 3; Metformin plus liraglutide +/- insulin+/- sulfonylurea	Drug: Metformin; Antidiabetic drugs; Other Names: Liraglutide; empagliflozin; Vildagliptin
EXPERIMENTAL: Group 4; Metformin plus empagliflozin +/- insulin +/- sulfonylurea	Drug: Metformin; Antidiabetic drugs; Other Names: Liraglutide; empagliflozin; Vildagliptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Alexandria University
• Collaborators: Eva Pharma

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 23, 2021
• Primary Completion (ACTUAL): September 30, 2021
• Study Completion (ANTICIPATED): September 30, 2022

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (ACTUAL): September 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Liver Diseases; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Liraglutide; Metformin; Empagliflozin; Vildagliptin
• Other Study ID Numbers: 0304932

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No