The Impact Of SGLT2 -I on Metabolic Dysfunction -Associated Steatotic Liver Disease In Patients With Type 2 Diabetes Mellitus

Fatty Liver, Nonalcoholic Clinical Trial

Official title: The Impact Of Sodium-Glucose Cotransporter 2 Inhibitors on Metabolic Dysfunction -Associated Steatotic Liver Disease In Patients With Type 2 Diabetes Mellitus

Status Not yet recruiting

Clinical Trial Summary

Study question 1:Could SGLT2-I improve hepatic fibrosis, steatosis, and inflammatory markers in type 2 diabetic patients with Metabolic associated steatotic liver disease Question 2:Which drug of SGLT2-I group is more effective in improving metabolic associated steatotic liver disease in type 2 diabetic patients?

Clinical Trial Description

patients will be derived from Endocrine or Hepatology outpatient clinic and who were primarily visiting for management of type 2 diabetes and other comorbidities.

The effect of the SGLT2-I on metabolic associated steatotic liver disease patients with Type two diabetes mellitus will be a prospective, open-label, parallel-groups, randomized clinical study to examine the effect of different types of SGLT2-I (dapagliflozin, empagliflozin,) when included in the standard treatment of Type two diabetes mellitus versus standard treatment without SGLT2-I for 24 weeks based on a predefined computer-generated number with a 1:1 allocation that will be concealed in patients with Type 2 diabetes mellitus and Metabolic associated steatotic liver disease Patients will be treated with combination therapy metformin and/or sulfonylurea and/or dipeptidyl peptidase 4 (DPP-4) inhibitors and/or insulin (control group), for whom treatment with SGLT2-I plus standard treatment for type 2 diabetes. (SGLT2-I group) will be indicated due to poor diabetes control

• The patients will subsequently be classified and treated by the lines of diabetes therapy (based on randomization into SGLT2-I or control group).

Baseline assessment (First visit)

All patients before randomization will be subjected to :

Detailed medical history including:

Demographic characteristics, Medications for glycemic control Compliance on medications Duration of Diabetes and presence of any comorbidity Diabetes complications.

Detailed clinical examinations including:

Height, weight, waist circumference Systolic blood pressure and diastolic blood pressure. Body mass index (BMI) is calculated with division of weight (in kg) by square of height (in meters).

3 - Laboratory investigations: Plasma glucose level Glycated hemoglobin (HbA1c) Blood urea and serum creatinine, Serum uric acid, Total bilirubin (mg/dL) Alanine aminotransferase (units/L), Aspartate aminotransferase(units/L) Albumin (units/L) Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglyceride, Plasma non-HDL-cholesterol was simply calculated by following formula: total cholesterol- HDL cholesterol.

Uric acid to cholesterol ratio is calculated with division of serum uric acid by HDL cholesterol.

The Uric acid to non-HDL cholesterol ratio is measured by the following formula: uric acid/non-HDL cholesterol.

Hepatitis B surface antigen, anti-hepatitis C and HIV I and II antibodies. Urine analysis and Albumin-to-creatinine ratio Complete blood counts Monocyte to high-density lipoprotein cholesterol ratio Neutrophil to lymphocyte ratio Platelet to lymphocyte ratio Lymphocyte to monocyte ratio Neutrophil-percentage-to-albumin ratio ECG 4-Other investigations will be including: Abdominal ultrasonography (Liver & spleen size, portal vein diameter) 5- Non-Invasive Testing of Hepatic steatosis/fibrosis: Using vibration-controlled transient elastography (FibroScan), Study visits All participants will be instructed about potential adverse drug reactions. Each participant will be asked to document all the symptoms that they will experience during the study period, whether related to drug or not.

Compliance and adverse events will be assessed by a verbal questionnaire. In both groups, adjustment of diabetes treatment will be carried out based on self-monitored blood glucose at weeks 4 and 8 by telephone consultation.

All participants will be instructed to restrict simple carbohydrates (avoid simple sugars, reduce rice preparations) and fat intake (reduce butter, ghee).

All participants will be advised to exercise (brisk walk) for at least 45 min a day for at least 5 days a week.

Participants will return to the outpatient hepatology clinic for follow-up visits at weeks 12 and 24.

All the participants, at baseline and at week 12, will receive uniform lifestyle modification instructions in accordance with the standards of diabetes management Anthropometry, physical examination results and biochemical measurements will be recorded for each participant in week 24.

Biochemical measurements at follow-up

Venous blood samples will be taken at week 24 in the morning after participants had fasted overnight for 12 h and the samples will be analyzed on the same day at the center laboratory of the hospital for the previous variables.

Vibration controlled transient elastography (VCTE) parameters

Liver stiffness measurement (LSM) by VCTE (related to liver fibrosis) and controlled attenuation parameter (CAP; related to liver fat) will be measured using Fibroscan a trained hepatologist who will be blinded to the drug allocation, clinical data, and biomarker data.

Study group:

At the end of the study, all the patients will be classified according to Type of treatment Control group (stander treatment of Type 2 diabetes mellitus without SGLT2-I ) SGLT2-I groups (stander treatment of Type 2 diabetes mellitus plus SGLT2-I )

SGLT2-I group will be sub-grouped to Group dapagliflozin: stander treatment of Type 2 diabetes mellitus plus dapagliflozin Group empagliflozin: stander treatment of Type 2 diabetes mellitus plus empagliflozin ;

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Fatty Liver
• Fatty Liver, Nonalcoholic
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

• NCT number: NCT06117137
• Study type: Interventional
• Source: Sohag University
• Contact: George Esmat Roshdy, Assistant lecturer
• Phone: 00201226866079
• Email: Goarge.kaldes@med.sohag.edu.eg
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 15, 2023
• Completion date: October 2024