Adding Semaglutide to SGLT2 Inhibitors Reduces Liver Enzymes in Patients with Type 2 Diabetes Complicated by Metabolic Dysfunction Associated Steatotic Liver Disease: A Retrospective Observational Study

Oct 8, 2025Internal medicine (Tokyo, Japan)

Adding Semaglutide to SGLT2 Inhibitors lowers liver enzyme levels in people with type 2 diabetes and fatty liver disease linked to metabolic problems

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Abstract

Semaglutide treatment resulted in a significant decrease in liver enzyme levels among 47 patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease.

Body weight decreased from 80.9 kg to 77.3 kg after six months of semaglutide treatment.
Body mass index reduced from 28.9 kg/m² to 27.7 kg/m² during the same period.
Glycated hemoglobin levels fell from 7.4% to 6.9%, indicating improved blood sugar control.
Aspartate aminotransferase levels decreased from 30.4 U/L to 26.3 U/L.
Alanine aminotransferase levels dropped from 42.4 U/L to 35.7 U/L.
No improvement was observed in the fibrosis-4 index, which assesses liver fibrosis.

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Objective To investigate the additive effects of semaglutide on liver function indicators in patients with type 2 diabetes mellitus (T2DM) complicated by metabolic dysfunction-associated steatotic liver disease (MASLD), who received sodium-glucose cotransporter 2 inhibitors (SGLT2-Is). Methods Liver function indicators at baseline were compared with those 6 months after the initiation of semaglutide. Patients Forty-seven patients (mean age, 56.2±10.4 years; 74.5% men) with T2DM complicated by MASLD who were prescribed SGLT2-Is continuously for at least 12 months were retrospectively selected. Results Six months of semaglutide treatment significantly decreased body weight (BW; 80.9±16.4 kg to 77.3±17.0 kg, p<0.001), body mass index (BMI; 28.9±4.5 kg/mto 27.7±4.6 kg/m, p<0.001), and the levels of glycated hemoglobin (HbA1c; 7.4% ±0.7% to 6.9% ±0.7%, p<0.001), aspartate aminotransferase (AST; 30.4±15.9 U/L to 26.3±12.5 U/L, p=0.014), alanine aminotransferase (ALT; 42.4±28.7 U/L to 35.7±22.8 U/L, p=0.022), and gamma-glutamyl transpeptidase (γ-GTP; 46.5±36.8 U/L to 38.0±30.0 U/L, p=0.001). The fibrosis-4 index, an indicator of liver fibrosis, did not improve. Changes in ALT levels were significantly correlated with changes in metabolic parameters, including BW (P=0.004), BMI (p=0.004), HbA1c (p=0.005), and triglycerides (p=0.011). Conclusion The addition of semaglutide to SGLT2-Is reduced liver enzyme levels in patients with T2DM complicated with MASLD. Future randomized controlled trials are needed to investigate the additive effects of semaglutide on MASLD in patients with T2DM receiving SGLT2-Is. 2 2

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Adding Semaglutide to SGLT2 Inhibitors Reduces Liver Enzymes in Patients with Type 2 Diabetes Complicated by Metabolic Dysfunction Associated Steatotic Liver Disease: A Retrospective Observational Study

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