Nonalcoholic fatty liver disease (NAFLD) is common in adults with Type 2 diabetes mellitus (T2DM), but comparative hepatic effects of sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain uncertain. A multicenter cohort study published in Frontiers in Endocrinology compared liver enzyme changes after initiation of SGLT2is or GLP-1 RAs in adults with T2DM and NAFLD.

The retrospective study included 705 adults enrolled between January 2020 and December 2024, including 381 patients receiving SGLT2 inhibitors and 324 receiving GLP-1 receptor agonists. Propensity score matching generated 243 well-matched treatment pairs with balanced baseline characteristics. The primary outcomes were 6-month changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Findings

• In the matched cohort, SGLT2 inhibitor therapy produced greater reductions in ALT compared with GLP-1 receptor agonist therapy (−10.55±12.66 vs. −7.28±15.34 U/L; P=0.011).
• AST reductions were also greater with SGLT2 inhibitors than with GLP-1 receptor agonists (−7.68±10.07 vs. −5.18±11.04 U/L; P=0.010).
• No significant between-group differences were observed for gamma-glutamyl transferase (GGT), body weight, glycemic control, or lipid profile changes.
• Multivariable regression analyses showed that SGLT2 inhibitor therapy independently predicted reductions in ALT (β=−3.34; P=0.009) and AST (β=−2.32; P=0.016).
• Weight change independently predicted AST reduction (β=0.22; P=0.016) but not ALT reduction.

The findings suggested that SGLT2 inhibitors may provide greater improvement in liver enzyme parameters than GLP-1 receptor agonists in adults with T2DM and NAFLD. ALT improvement appeared independent of weight reduction in the adjusted analyses.