In patients with type II diabetes mellitus (T2DM) and obesity, an excess plasma-free fatty acid is found with an associated increased lipid accumulation in adipocytes and liver tissue. Lipid droplet accumulation in the hepatocytes is an initial step in the development of metabolic dysfunction associated steatotic liver disease (MASLD. Insulin resistance, which is associated with T2DM, mediates the inflammation of these lipids, resulting in the progression of MASLD to metabolic dysfunction associated steatotic hepatitis (MASH). Hence, in T2DM, obesity, and MASLD, changes in the lipid profile occur, and they are interrelated.

In this study, we aim to assess improvement in the lipidomic, its associated metabolic changes and evaluate the co-regulated genes in the liver tissue among patients with MASLD with intervention with GLP-1 RA, which has shown to benefit T2DM and obesity.

The study involves patients with a diagnosis of MASLD by histology and have diabetes/obesity. The 'omics' ( lipidomics, proteomics, metabolites, and inflammatory profiles and transcriptomics) data of liver tissue and plasma of patients will be compared between patients who have received 1 year of GLP-1 treatment with those who did not have GLP-1 agents.

The study will evaluate the changes in different 'omics' and metabolites in the liver tissue following the use of GLP-1 agents in these patients

Inclusion Criteria:

• known diagnosis of MASLD by histology, also have diabetes/ obesity
• on treatment with GLP-1 RA at stable dose

Exclusion Criteria:

• unable to have a liver biopsy, recent change in medication for diabetes or hyperlipidemia
• on immunosuppression, liver or kidney transplant
• pregnancy

known diagnosis of MASLD by histology, also have diabetes/ obesity