Efficacy of Empagliflozin and Pioglitazone in Diabetic Patients With NAFLD

Phase 4

Not yet recruiting

• Conditions: Non-Alcoholic Fatty Liver Disease; Type2diabetes
• Interventions: Drug: Pioglitazone 15mg; Drug: Empagliflozin 10 MG; Drug: Metformin

• Registration Number: NCT05942963
• Lead Sponsor: Jinnah Postgraduate Medical Centre

Brief Summary

This clinical trial will yield results about the therapeutic effect of combining pioglitazone with SGLT2i in people suffering from NAFLD associated with T2DM. Study participants will be asked to fill out a few questions on proforma that will obtain demographic information as well as information relating to their health. In addition, some blood tests will be done following standard procedures.

Detailed Description

This is a randomized clinical trial conducted to compare the efficacies of pioglitazone and empagliflozin in people suffering from NAFLD associated with T2DM.

Randomization will be done using card randomization. Four different color-coded cards will be kept. Any card will be randomly picked for the patient fulfilling inclusion criteria and will be treated according to the allocated treatment arm mentioned on the card

Written informed consent will be obtained from the immediate attendant of the patient. All ethical considerations will be followed.

Our research has been approved by Jinnah Sindh Medical University, Karachi. For this approval, the investigators have made every effort to ensure the confidentiality of research data collected from all our participants in this survey. The information collected will be stored with the investigators only in the form of de-identified information and will be retained in a secure place under lock and key. Any results that will be generated will be presented on a collective basis, and will not contain the participants name or any other personal details.

Data entry and analysis will be done using SPSS Software version 23. Study analysis will be done using the principle of intention to treat. The mean scores will be compared pre and post-intervention using paired t-test. The association of age, gender, and grade of fatty liver will be compared with different groups using correlation and regression models. All analyses will be at a confidence Interval of 95% and a p-value \<.05.

Study Timeline

• Study First Submitted: 2023-06-16
• Status Verified: 2023-07
• Study First Submitted QC: 2023-07-11
• Last Update Submitted: 2023-07-11
• Study First Posted: 2023-07-12
• Last Update Posted: 2023-07-12
• Study Start: 2023-10
• Primary Completion: 2024-04
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• T2DM patients with NAFLD glycated
• APRI scores of more than 1.5

Exclusion Criteria

• Patients having type 1 diabetes
• evidence of advanced/decompensated cirrhosis (on the basis of a Child-Pugh score of more than 7 and MELD of more than 15)
• hepatocellular carcinoma (evidence on ultrasound or alpha-fetoprotein)
• patient suffering from acute or chronic hepatitis
• biliary disease
• HIV
• hemochromatosis
• autoimmune conditions (alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease)
• renal dysfunction with GFR [eGFR] <30 mL/min/1.73m2
• history of alcohol ( male >30 g/d and female;20 g/d)
• history of cancer or undergoing treatment for cancer,
• use of amiodarone, tamoxifen, sodium valproate, corticosteroids, methotrexate, ursodeoxycholic acid, S-adenosyl methionine, betaine, silymarin, gemfibrozil
• using supplements including vitamin E, vitamin C, zinc, and selenium or antioxidant agents over the last 3 months
• history of cardiovascular events within the past 3 months
• pregnancy or breastfeeding
• contraindications to empagliflozin use (history of recurrent urogenital infections, current or previous gangrene, or hypersensitivity reaction to the molecule)
• history of bladder cancer
• morbid obesity (BMI greater than 35).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Group C	Pioglitazone 15mg	SOC+ Pioglitazone
Group A	Empagliflozin 10 MG	SOC+ Empagliflozin + Pioglitazone
Group A	Pioglitazone 15mg	SOC+ Empagliflozin + Pioglitazone
Group D	Metformin	SOC only
Group B	Empagliflozin 10 MG	SOC +Empagliflozin
Group A	Metformin	SOC+ Empagliflozin + Pioglitazone
Group B	Metformin	SOC +Empagliflozin
Group C	Metformin	SOC+ Pioglitazone

Primary Outcome Measures

Name	Time	Method
A change in liver steatosis will be assessed through fibro CAP score.	Will be assessed at 168th day post enrollment.	Fibro-controlled attenuation parameter (fibro CAP). The parameter range is commonly between 100 and 400 dB/m, and the greater the reading worse will be the outcome.

Secondary Outcome Measures

Name	Time	Method
Change in Body mass index	at enrollment.	Body mass index. lower the levels better the outcome.
Change in body mass index	at day 252 post enrollment.	body mass index. lower the levels better the outcome.
change in liver fibrosis will be assessed through the NFS Score.	at day 252 post enrollment.	NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)
Change in hepatic steatosis through the FLI score.	at day 252 post enrollment.	Fatty liver index (FLI). Lower the value better the outcome
Change in waist circumference	at day 252 post enrollment.	waist circumference. lower the levels better the outcome.
Change in HbA1c	at day 252 post enrollment.	hemoglobin A1c (HbA1c).lower the levels better the outcome.
change in SF-36 scores	Quality of life will be assessed at day 252 post enrollment.	36-Item Short Form Survey (SF-36) assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. A higher score defines a more favorable health state.
change in liver fibrosis will be assessed through the FIB-4 index.	at day 252 post enrollment.	Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).
change in liver fibrosis will be assessed through the APRI Score	at 168th day post enrollment.	AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)
Change in the LFT.	at day 252 post enrollment.	Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .
Change in random blood sugar	at day 252 post enrollment.	random blood sugar. lower the levels better the outcome.
change in liver fibrosis will be assessed through the APRI Score.	at day 252 post enrollment.	AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)
Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.	at day 252 post enrollment.	homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome.
Change in weight	at day 252 post enrollment.	weight. lower the levels better the outcome.

Trial Locations

Locations (1)

Medical ICU, Jinnah Postgraduate Medical Centre; 🇵🇰 Karachi, Sindh, Pakistan