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Effects of GLP1-RAs and SGLT2i on liver steatosis and fibrosis in MASLD with type 2 diabetes

Minerva Med. 2026 Jul 26. doi: 10.23736/S0026-4806.26.09922-2. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in individuals with type 2 diabetes mellitus (T2DM). MASLD ranges from simple liver steatosis to metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. New glucose-lowering agents have demonstrated benefits beyond glycemic regulation. This study assesses the effects of receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) on metabolic parameters, hepatic steatosis, and fibrosis in patients with MASLD and T2DM.

METHODS: Prospectively, 192 patients were enrolled: 132 added therapy with one novel glucose-lowering drug (GLP-1RA or SGLT2i) or their combination, and 60 patients continued with other glucose-lowering therapies (such as sulfonylureas, PPAR-γ agonists, DPP-4 inhibitors, metformin or insulin). Metabolic parameters, fibrosis indices (APRI, FIB-4, NFS, stiffness), and steatosis assessed by ultrasound-based attenuation imaging (ATT), were evaluated at baseline, 6 and 12 months.

RESULTS: The four treatment groups had comparable biochemical profiles. At 6 months, significant reductions were observed in the ALT, AST, GGT, and ALP levels (P<0.01). Both GLP-1RA and SGLT2i significantly improve glycemic control at 6 and 12 months; the reduction in HbA1c was associated with a decrease in serum cholesterol (statistically significant in the SGLT2i group). Non-invasive fibrosis scores (FIB-4, APRI, NFS) showed no significant changes; however, NFS showed modest improvement in the SGLT2i group. Liver stiffness values decreased significantly after 12 months in GLP-1RA, SGLT2i, or combination therapy groups. ATT consistently improved hepatic steatosis.

CONCLUSIONS: GLP-1RA and SGLT2i improve glycemic control and reduce hepatic steatosis and stiffness in patients with MASLD and T2DM.

PMID:42507338 | DOI:10.23736/S0026-4806.26.09922-2

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