Comparative Effects of Aspirin, Metformin and SGLT2 Inhibitors on Liver Enzymes, Lipid Profile, and FibroScan Findings in Non-Alcoholic Fatty Liver Disease

Comparison Between the Effect of Aspirin, Metformin, and SGLT2 Inhibitor Intake in Non-Alcoholic Fatty Liver on Liver Enzymes, Lipid Profile, and the Results of FibroScan

Non-alcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is a common hepatic manifestation of metabolic dysfunction and may progress from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma.

This randomized clinical trial evaluated and compared three pharmacological approaches with different mechanisms of action: low-dose aspirin as an anti-inflammatory and antiplatelet therapy, dapagliflozin as a sodium-glucose cotransporter-2 (SGLT2) inhibitor with metabolic effects, and metformin as an insulin-sensitizing therapy.

The study assessed their effects on liver enzymes, lipid profile, and FibroScan-derived measures of hepatic steatosis and liver stiffness over a 6-month treatment period.

This was a single-center, open-label, parallel-group randomized controlled clinical trial conducted over 6 months in adults diagnosed with non-alcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD).

Participants were randomly allocated to one of three treatment groups:

• Aspirin group: aspirin 100 mg orally once daily for 6 months.
• Dapagliflozin group: dapagliflozin 10 mg orally once daily for 6 months.
• Metformin group: metformin 1000 mg orally once daily for 6 months.

The study was designed to compare the hepatic and metabolic effects of anti-inflammatory/antiplatelet therapy, SGLT2 inhibition, and insulin-sensitizing therapy in patients with NAFLD/MASLD.

Participants underwent clinical and laboratory assessment at baseline and after 6 months of treatment. Laboratory assessments included liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), together with lipid-profile parameters, including total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C).

Hepatic steatosis and liver stiffness were assessed noninvasively using vibration-controlled transient elastography (FibroScan). The controlled attenuation parameter (CAP, dB/m) was used to assess hepatic steatosis, while liver stiffness measurement (LSM, kPa) was used to assess liver stiffness/fibrosis-related changes.

The main study outcomes included changes from baseline to 6 months in FibroScan-derived CAP and LSM values, liver enzymes, and lipid-profile parameters. Additional metabolic and clinical outcomes included body weight, waist circumference, and other relevant metabolic indicators where available.

Statistical Analysis: Continuous variables were summarized using appropriate descriptive statistics. Within-group changes from baseline to 6 months were evaluated using paired statistical tests as appropriate. Comparisons among the three treatment groups were performed using analysis of variance (ANOVA) or corresponding non-parametric tests, as applicable. Analysis of covariance (ANCOVA) adjusting for baseline values was used when baseline differences were present. Appropriate post-hoc pairwise comparisons were performed where required. All statistical tests were two-sided, and a p-value <0.05 was considered statistically significant.

Inclusion Criteria: if one or more the following are present:

• Diabetes mellitus, unless receiving only Dapagliflozin for treatment.
• Adult individuals (18-65 years) with a clinical diagnosis of NAFLD based on liver ultrasound
• No history of alcohol consumption or consumption within 3 months.
• Absence of other liver diseases.
• No significant renal or gastrointestinal issues that could interfere with treatment.

Exclusion Criteria:Patients were excluded from our study if one or more the -following are present:

• Pregnancy or breastfeeding.
• Active chronic viral hepatitis or autoimmune liver disease.
• History of gastrointestinal bleeding or other contraindications for Aspirin.
• Severe renal insufficiency.
• Alcohol intake