Advanced liver disease remains an important complication in people with Type 2 diabetes mellitus (T2DM), yet randomized trials of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have not been powered to assess long-term liver outcomes. A systematic review and exploratory meta-analysis published in Frontiers in Endocrinology evaluated comparative real-world evidence on advanced liver outcomes associated with GLP-1RA use in adults with T2DM.
The review included peer-reviewed comparative cohort studies identified through PubMed/MEDLINE and Embase searches, with updated evidence screening through April 25, 2026. The analysis emphasized active-comparator designs and clinically advanced liver endpoints, including incident cirrhosis and composite serious liver outcomes.
Twelve eligible comparative studies were identified. Four studies comparing GLP-1RAs with dipeptidyl peptidase-4 (DPP-4) inhibitors were considered sufficiently comparable for exploratory random-effects meta-analysis within the predefined active-comparator outcome stratum.
Findings
- The primary Hartung-Knapp pooled analysis showed a lower risk of incident cirrhosis or composite serious liver events with GLP-1RAs versus DPP-4 inhibitors (HR 0.85; 95% CI 0.74-0.98).
- A secondary restricted maximum-likelihood (REML) analysis produced a narrower confidence interval (95% CI 0.79-0.93), with no observed statistical heterogeneity (I²=0%).
- Outcome definitions and comparator strategies varied across studies, limiting direct comparability between cohorts.
- Evidence certainty was rated very low because all included studies were observational and residual confounding and healthcare-engagement bias could not be excluded.
The analysis suggested a directionally favorable association between GLP-1RA use and advanced liver outcomes in adults with T2DM. However, the findings should be interpreted cautiously because the available evidence was observational and not sufficient to establish causality.
