What question did this study set out to answer?

To compare the effects of SGLT2 inhibitors and GLP-1 receptor agonists on liver enzyme levels in patients with type 2 diabetes and NAFLD.

June 6, 2026Frontiers in Endocrinology0 citationsOpen Access

Effects of SGLT-2 inhibitors and GLP-1 receptor agonists on liver function in patients with non-alcoholic fatty liver disease and type 2 diabetes

WGWancheng Guo WLWenhe Li XLXianlin Li

Key Points

To compare the effects of SGLT2 inhibitors and GLP-1 receptor agonists on liver enzyme levels in patients with type 2 diabetes and NAFLD.
Multicenter cohort study involving 705 subjects with T2DM and NAFLD, with PSM for baseline equivalence.
Main measurements included changes in ALT and AST levels over 6 months from baseline.
Multivariate linear regression analysis identified independent predictors for liver enzyme changes.
In the matched cohort, SGLT2 inhibitors led to greater reductions in ALT (-10.55 U/L vs. -7.28 U/L, p=0.011) and AST (-7.68 U/L vs. -5.18 U/L, p=0.010) compared to GLP-1 receptor agonists.
Multivariable regression indicated SGLT2 inhibitors were significantly associated with ALT reduction (β = -3.34, p=0.009) and AST reduction (β = -2.32, p=0.016).
Weight change was positively associated with AST reduction (β = 0.22, p=0.016), but not with ALT.

Abstract

Background The goal was having the comparisons be direct when it came to seeing how much of a help the sodium-glucose co transporter - 2 inhibitors (SGTL2is) compared to the glucagon-like peptide-1 receptor agonists (GLP-1RAs) were in regard to how the liver enzymes performed within people having type 2 diabetes (T2D) along with nonalcoholic fatty liver disease (NAFLD), a condition characterized by excessive fat accumulation in the liver without alcohol overconsumption. Methods A total of 705 subjects with T2DM and NAFLD at time of first SGLT2is (n=381) or GLP-1RAs (n=324) enrolment in this multicentre posterior cohort study from 01/2020-12/2024. Baseline characteristics were made equivalent via PSM via a 1: 1 NN match and a 0. 2 SD match clamp. The main measurement was the difference in alanine amino transferase (ΔALT) and aspartate aminotransferase (ΔAST) from the beginning and 6 months. And other result was about the change in metabolic parametres. The independent predictors of liver-enzyme change came from the multivariate linear regression analysis. Results After PSM, 243 well-matched pairs were successfully identified, with baseline characteristics acceptably balanced (standardized differences 0.2 for all covariates and 0.1 for most covariates). In the matched cohort, SGLT2is treatment was associated with significantly greater reductions in ALT (ΔALT: -10.55 ± 12.66 vs. -7.28 ± 15.34 U/L, p=0.011) and AST (ΔAST: -7.68 ± 10.07 vs. -5.18 ± 11.04 U/L, p=0.010) compared to GLP-1RAs treatment. No significant differences were observed for changes in GGT, body weight, glycemic control, or lipid profiles between groups. Multivariable regression analysis revealed that SGLT2is treatment was independently associated with reductions in both ALT (β = -3.34, p=0.009) and AST (β = -2.32, p=0.016). Weight change was independently associated with AST reduction (β = 0.22, p=0.016) but not with ALT reduction. Conclusion SGLT2is were associated with greater ALT and AST reductions than GLP-1RAs in T2D patients with NAFLD, with ALT improvement independent of weight loss, suggesting potential direct hepatoprotective effects.

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