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

NCT07391267 | Not Yet Recruiting

• 1 other identifier: ILBS-CKD-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Time to first occurrence of a composite primary outcome event defined as persistent eGFR decline of greater than or equal to 50 percentage from trial start, reaching ESRD, death from kidney disease or death from cardiovascular disease.

  3 months, 6 months, 12 months,18 months and 24 months

Secondary Outcomes (23)

• Annual rate of change in eGFR (chronic kidney disease - epidemiology collaboration (CKD-EPI))

  3 months, 6 months, 12 months,18 months and 24 months

• ime to first occurrence of a composite cardiovascular major adverse cardiovascular event (MACE) endpoint consisting of: Non-fatal myocardial infarction, non-fatal stroke, and cardiovascular (CV) death

  3 months, 6 months, 12 months,18 months and 24 months

• Time to occurrence of all-cause death

  3 months, 6 months, 12 months,18 months and 24 months

• Change in eGFR and proteinuria.

  3 months, 6 months, 12 months,18 months and 24 months

• Annual rate of change in eGFR (CKD-EPI) (chronic eGFR slope)

  3 months, 6 months, 12 months,18 months and 24 months

Study Arms (2)

Standard Medical Treatment (SMT)

ACTIVE COMPARATOR

Control arm : Participants in this arm will receive Placebo with Standard Medical Treatment (SMT).

Other: Placebo; Other: Standard medical treatment

Semaglutide with Standard Medical Treatment

EXPERIMENTAL

Semaglutide with Standard Medical Treatment: Participants in this arm will receive Standard medical treatment and oral semaglutide starting from 3mg dose daily that gradually increases upto 14mg dose daily for 6 months.

Drug: Semaglutide Oral Tablet; Other: Standard medical treatment

Interventions

Placebo OTHER

Placebo will be given in the same manner.

Standard Medical Treatment (SMT)

Standard medical treatment OTHER

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

Semaglutide with Standard Medical Treatment; Standard Medical Treatment (SMT)

Semaglutide Oral Tablet DRUG

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.

Semaglutide with Standard Medical Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age above or equal to 18 years at the time of signing informed consent. 2.Diagnosed with type 2 diabetes mellitus 3.HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol) 4.Renal impairment defined either by:
• serum creatinine-based eGFR greater than or equal to 50 and less than or equal to 75 mL/min/1.73 m\^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g or

You may not qualify if:

• Documented causes of chronic liver disease other than non-alcoholic fatty liver disease (NAFLD)
• Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A).
• Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation.
• Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).
• Treatment with vitamin E (at doses greater than or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose from time of biopsy until screening.
• Treatment with GLP-1 RAs in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, any treatment with GLP-1 RAs from time of biopsy until screening (V2A).
• Treatment with glucose-lowering agent(s) (other than GLP-1 RAs), lipid-lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.
• Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening.
• Presently classified as being in New York Heart Association (NYHA) Class IV heart failure
• Planned coronary, carotid or peripheral artery revascularisation
• Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis 13 Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupildilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dr Chandani Bhagat, DM

CONTACT

01146300000; chandani.bhagat@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patient and Investigator

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: February 5, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 5, 2026

Record last verified: 2025-12

Locations

IN (1)