Pathogenesis of Chronic Kidney Disease Associated With Metabolic Dysfunction- Associated Fatty Liver Disease (MAFLD) and Treatment Response of Oral Semaglutide.

Summary

This project aims to investigate how Chronic Kidney Disease (CKD) develops and progresses in patients who also have Non-Alcoholic Fatty Liver Disease (NAFLD) and to evaluate whether oral semaglutide (a GLP-1 receptor agonist) can slow or prevent this progression.

NAFLD and CKD frequently coexist due to shared mechanisms such as insulin resistance, inflammation, oxidative stress, dyslipidemia, and metabolic syndrome. Because of these overlapping pathways, a single therapy targeting both organs may offer major benefits.

Semaglutide is known to reduce liver fat, improve inflammation and fibrosis, promote weight loss, and provide renal protection. This project will test whether adding oral semaglutide to standard care leads to better kidney and liver outcomes than standard care alone.

The study is designed as a randomised controlled trial conducted at ILBS, enrolling adults having NAFLD with CKD (with specific eGFR and albuminuria criteria). Participants will be followed for 2 years, with regular assessment of kidney function (eGFR, ACR), liver health (FibroScan, ALT/AST), metabolic parameters, and cardiovascular outcomes.

A parallel animal study in mice with diet-induced fatty liver disease will validate mechanistic findings through liver and kidney histology, gene expression, metabolic tests, and biochemical markers after semaglutide treatment.

Expected outcome: To demonstrate that semaglutide slows CKD progression and improves NAFLD, supporting its use as a therapeutic option for patients with coexisting both conditions.

Conditions

• Chronic Kidney Diseases
• MAFLD

Interventions

DRUG

Semaglutide Oral Tablet

GLP1-R agonists GLP1-R agonists (GLP1-RAs) are novel potent antidiabetic agents with proven efficacy in reducing major adverse cardiovascular events. Besides their glucose-lowering action, their beneficial hepatic effects may be related to the influence on the AMPK/mTOR pathway. Semaglutide was associated with significant decreases in body weight, alanine aminotransferase, liver steatosis, and stiffness.GLP1-RAs may also improve histologic features on NAFLD, such as liver fat deposition, steatohepatitis, and fibrosis. GLP1-RAs have shown benefits in preventing the development or halting the progression of CKD. It also promotes antioxidative and anti-inflammatory actions may be among the determining factors in this renoprotective effect, together with weight loss, blood pressure, and glucose-lowering.

OTHER

Placebo

Placebo will be given in the same manner.

OTHER

Standard medical treatment

Standard medical treatment- 1. Lifestyle first - weight loss , caloric restriction, increased aerobic + resistance exercise, treat obesity and metabolic syndrome. 2. Optimize blood-pressure control and use RAAS blockade when indicated (ACE inhibitor or ARB) to reduce albuminuria and slow CKD progression . 3. Treat dysglycaemia and favour drug classes with kidney + liver benefit when appropriate * SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin) - recommended for people with T2D + CKD * GLP-1 receptor agonists (e.g., semaglutide) 4. Lipid management / statins - treat according to CV risk 5. Consider established liver-directed agents when appropriate 6. Pioglitazone (thiazolidinedione) and vitamin-E 7. Standard CKD supportive care - salt and fluid management, correction of metabolic acidosis, anaemia and mineral bone abnormalities as per CKD stage; immunize and address CV risk factors aggressively 8. Avoid hepatotoxic drugs / review medications

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-01

Primary Completion

2028-12-31

Completion

2028-12-31

Countries

• India

Study Locations