Health Condition 1: N182- Chronic kidney disease, stage 2 (mild) Health Condition 2: N183- Chronic kidney disease, stage 3 (moderate) Health Condition 3: K760- Fatty (change of) liver, not elsewhere classified
Conditions
Interventions
Intervention1: Semaglutide with Standard Medical Treatment: Oral semaglutide starting from 3mg dose daily that gradually increases upto 14mg dose daily for 6 months.Standard Medical Treatment
Control
Sponsors
Indian Council of Medical Research
Department of Health Research
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age 18 years or above at the time of signing informed consent. 2. Diagnosed with type 2 diabetes mellitus. 3. HbA1c less than or equal to 10 percent. 4. Renal impairment defined as either of the following: a. Estimated glomerular filtration rate between 50 and 75 mL per minute per 1 point 73 square meter calculated using CKD EPI equation and urine albumin creatinine ratio more than 300 mg per g and less than 5000 mg per g. OR b. Estimated glomerular filtration rate between 25 and 50 mL per minute per 1 point 73 square meter calculated using CKD EPI equation and urine albumin creatinine ratio more than 100 mg per g and less than 5000 mg per g. 5. On stable treatment with maximum labelled or tolerated dose of renin angiotensin aldosterone system blocking agent including angiotensin converting enzyme inhibitor or angiotensin receptor blocker unless contraindicated or not tolerated. Dose must be stable for at least 4 weeks prior to screening laboratory assessment.
Exclusion criteria
Exclusion criteria: 1. Documented causes of chronic liver disease other than non-alcoholic fatty liver disease (NAFLD) 2. 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). 3. Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation. 4. 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)). 5. 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. 6. 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). 7. 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. 8. Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations 9. Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening. 10. Presently classified as being in New York Heart Association (NYHA) Class IV heart failure 11. Planned coronary, carotid or peripheral artery revascularisation 12. 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.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Annual rate of change in eGFR (chronic kidney disease - epidemiology collaboration (CKD-EPI))Timepoint: 3 months, 6 months, 12 months,18 months and 24 months;Time 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) deathTimepoint: 3 months, 6 months, 12 months,18 months and 24 months;Time to occurrence of all-cause deathTimepoint: 3 months, 6 months, 12 months,18 months and 24 months;Time to occurrence of each of the individual components of the primary composite endpoint and of the confirmatory secondary MACE endpointTimepoint: 3 months, 6 months, 12 months,18 months and 24 months;Annual rate of change in eGFR (CKD-EPI) (chronic eGFR slope)Timepoint: 3 months, 6 months, 12 months,18 months and 24 months;Change in eGFR (CKD-EPI) and cystatin CTimepoint: 3 months, 6 months, 12 months,18 months and 24 months;Change in albumin creatinine ratio(ACR),bodyweight,HbA1c,SBP,DBP,number of hypoglycemic episodes,liver histology and renal histology in the animal model,LSM,ELF,ALT,AST,CAP,FAST,TG,LDL,hsCRPTimepoint: 3 months, 6 months, 12 months,18 months and 24 months;Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No)Timepoint: 3 months, 6 months, 12 months,18 months and 24 months | — |
Primary
| Measure | Time frame |
|---|---|
| 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.Timepoint: 3 months, 6 months, 12 months,18 months and 24 months | — |
Countries
India
Contacts
Public ContactDr Rajan Mathur
Institute of Liver and Biliary Sciences
Outcome results
None listed