Incremental effects of SGLT2 inhibitors, GLP-1 receptor agonists, and pioglitazone in type 2 diabetes and MASLD across Asian study settings: a systematic review and meta-analysis
Abstract
Objective: We evaluated the incremental hepatic and metabolic effects of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or pioglitazone to comparable background glucose-lowering therapy in Asian adults with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science through 30 June 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Eligible trials evaluated the addition of a study drug to background glucose-lowering management that was comparable between randomized groups and either remained stable or followed a prespecified adjustment protocol. Changes from baseline in alanine aminotransferase (ALT) and glycated hemoglobin (HbA1c) were coprimary outcomes. Secondary outcomes included aspartate aminotransferase, gamma-glutamyl transferase, magnetic resonance imaging-proton density fat fraction, liver stiffness, fibrosis-4 index, fasting plasma glucose, lipid parameters, body mass index, serum adiponectin, and systolic blood pressure. Random-effects pairwise meta-analyses were performed, and GRADE certainty was assessed for the two coprimary outcomes. Safety outcomes were synthesized narratively because reporting was heterogeneous and frequently incomplete.
Results: We included eleven randomized trials: 692 participants were randomized…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 692 participants or records.
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