Liver gains beyond glycemic control: GLP-1 vs. SGLT2 in metabolic dysfunction-associated steatohepatitis (MASH): A real-world data analysis.

BACKGROUND

Metabolic dysfunction associated steatohepatitis (MASH) is a progressive liver disease associated with metabolic syndrome. While both GLP-1 receptor agonists and SGLT2 inhibitors offer cardiometabolic benefits, their comparative impact on liver-related outcomes in MASH remains unclear.

OBJECTIVE

To compare the incidence of cirrhosis, hepatocellular carcinoma (HCC), and changes in liver enzyme profiles in patients with MASH treated with GLP-1 receptor agonists versus SGLT2 inhibitors.

METHODS

This retrospective cohort study used de-identified electronic health records from the TriNetX network. Adults with MASH were grouped into GLP-1 receptor agonist users (n=19,421) or SGLT2 inhibitor users (n=12,772). After 1:1 propensity score matching on demographics, BMI, diabetes, liver enzymes, and substance use, 10,803 patients remained in each cohort. Patients with overlapping use of both drug classes or with preexisting cirrhosis, fibrosis, HCC, viral hepatitis, or alcoholic liver disease were excluded. Outcomes included incidence of cirrhosis, HCC, and liver enzyme normalization (ALT <60 U/L, AST <60 U/L, GGT ≤140 U/L). Risk estimates and hazard ratios were calculated using TriNetX analytics; p<0.05 was considered significant.

RESULTS

After matching, 10,803 patients were included in each cohort. Compared to SGLT2 inhibitors, the GLP-1 cohort showed significantly lower risks of cirrhosis (5.8 %¦vs. 17.3 %; HR: 0.31, 95 % CI: 0.29-0.34), HCC (0.4 %¦vs. 1.8 %; HR: 0.25, 95 % CI: 0.18-0.34), and elevated GGT (5.4 %¦vs. 6.8 %; HR: 0.80, 95 % CI: 0.72-0.89). Liver enzyme control (ALT and AST < 60 U/L) was also more favorable in the GLP-1 group (p < 0.001).

CONCLUSION

In this large real-world cohort of patients with MASH, GLP-1 receptor agonists were associated with significantly better liver-related outcomes compared to SGLT2 inhibitors. These findings support the potential hepatoprotective role of GLP-1 agents and highlight their promise in managing MASH beyond glycemic control.