Clinical Report: Impact of SGLT-2 Inhibitors versus GLP-1 Receptor Agonists on Hepatic Function

Overview

This study compares the effects of SGLT-2 inhibitors and GLP-1 receptor agonists on liver enzyme levels in patients with type 2 diabetes and non-alcoholic fatty liver disease. SGLT-2 inhibitors were found to significantly reduce alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to GLP-1 receptor agonists.

Background

Non-alcoholic fatty liver disease (NAFLD) is prevalent among individuals with type 2 diabetes (T2D), affecting approximately 60-80% of this population. The coexistence of T2D and NAFLD increases the risk of cardiovascular events and all-cause mortality. Effective management of NAFLD is crucial for improving long-term outcomes in T2D patients.

Data Highlights

Key Findings

• SGLT2 inhibitors resulted in a greater reduction in ALT compared to GLP-1 receptor agonists (p=0.011).
• SGLT2 inhibitors also led to a greater reduction in AST compared to GLP-1 receptor agonists (p=0.010).
• Weight change was independently associated with AST reduction but not with ALT reduction.
• Baseline characteristics were well-matched after propensity score matching, ensuring reliable comparisons.
• Both drug classes did not show significant differences in changes in GGT, body weight, glycemic control, or lipid profiles.

Clinical Implications

The findings suggest that SGLT2 inhibitors may offer superior hepatoprotective effects compared to GLP-1 receptor agonists in managing liver function in T2D patients with NAFLD. Clinicians should consider these differences when selecting treatment options for patients with these comorbidities.

Conclusion

SGLT2 inhibitors demonstrate a more significant impact on liver enzyme reduction than GLP-1 receptor agonists in patients with T2D and NAFLD, highlighting their potential role in hepatoprotection.

Related Resources & Content

1. Conexiant, Source, 2023 -- SGLT2 Inhibitors Linked to Better Outcomes in Diabetes and Cirrhosis
2. Frontiers in Endocrinology, Source, 2023 -- Clinical efficacy, safety, and predictors of treatment response to SGLT2 versus DPP-4 inhibitors in type 2 diabetes: a retrospective comparative study
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4. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD), 2024
5. Frontiers in Endocrinology — Glucagon-like peptide-1 receptor agonists and advanced liver outcomes in type 2 diabetes: a systematic review and exploratory meta-analysis
6. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes—2026
7. Clinical Assessment and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease | AASLD
8. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)
9. Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis | New England Journal of Medicine
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11. Efficacy of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists in managing MALFD: a meta-analysis of randomized controlled trials | BMC Gastroenterology | Springer Nature Link
12. Evaluating the Comparative Effectiveness of Sodium-Glucose Transporter 2 Inhibitors (SGLT-2i) on Liver Enzymes in Patients With Nonalcoholic Fatty Liver Disease: A Comprehensive Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials - PMC
13. Liver gains beyond glycemic control: GLP-1 vs. SGLT2 in metabolic dysfunction-associated steatohepatitis (MASH): A real-world data analysis - PubMed