Oral Semaglutide Aims to Slow Chronic Kidney Disease Progression and Improve NAFLD in a 2-Year RCT

Chronic Kidney Disease (CKD) and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) frequently coexist, driven by shared pathologies like insulin resistance, inflammation, oxidative stress, and dyslipidemia. Current standard care often addresses these conditions separately, leaving a gap for therapies that can target both organ systems simultaneously. GLP-1 receptor agonists like semaglutide are known to reduce liver fat, improve inflammation, promote weight loss, and provide renal protection, suggesting a potential dual benefit. This project aims to explore this synergistic therapeutic approach.

This randomized controlled trial will enroll adults with NAFLD and CKD (specific eGFR and albuminuria criteria) at ILBS. Participants will receive either oral semaglutide plus standard care or standard care alone for 2 years. Primary endpoints include kidney function (eGFR, ACR), liver health (FibroScan, ALT/AST), metabolic parameters, and cardiovascular outcomes. A parallel animal study in diet-induced fatty liver disease mice will investigate mechanistic insights through liver and kidney histology, gene expression, metabolic tests, and biochemical markers after semaglutide treatment.

This project outlines the design of a randomized controlled trial and a parallel animal study; therefore, no specific findings or numerical results are available yet. The primary objective is to demonstrate that oral semaglutide can slow the progression of Chronic Kidney Disease and improve Metabolic Dysfunction-Associated Fatty Liver Disease in patients with both conditions. The study is designed to show that adding oral semaglutide to standard care leads to better kidney and liver outcomes than standard care alone over 2 years. Mechanistic validation in mice with diet-induced fatty liver disease will involve assessing liver and kidney histology, gene expression, metabolic tests, and biochemical markers post-treatment. The expectation is that semaglutide's known benefits in reducing liver fat, improving inflammation, and promoting weight loss will translate into significant improvements in both renal and hepatic parameters, supporting its use as a therapeutic option.