Abstract / Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve weight, glycemic control, and cardiometabolic risk factors, but randomized trials have not been powered to determine effects on advanced liver outcomes. We conducted a systematic review and exploratory meta-analysis of peer-reviewed comparative real-world cohort studies in adults with type 2 diabetes (T2D), emphasizing active-comparator designs, clinically advanced liver endpoints, and transparent limits of causal inference. PubMed/MEDLINE and Embase were searched with citation chasing and an updated PubMed/MEDLINE search through 25 April 2026; this evidence-identification strategy was focused rather than exhaustive. Twelve eligible comparative studies were included. In the predefined active-comparator outcome-family stratum, four studies comparing GLP-1RAs with DPP-4 inhibitors were sufficiently exchangeable for exploratory random-effects synthesis of incident cirrhosis or composite serious liver events. The primary Hartung-Knapp small-sample interval for the pooled estimate was HR 0.85 (95% CI 0.74-0.98); the conventional REML interval was narrower and is reported as a secondary reference estimate (95% CI 0.79-0.93; I²=0%; REML τ²=0.000). Certainty of evidence was rated very low because all included studies were observational, outcome definitions and comparator strategies varied, and residual confounding and healthcare-engagement bias could not be excluded. GLP-1RA use shows a directionally favorable signal for advanced liver outcomes in T2D, but the evidence should be interpreted as hypothesis-supporting rather than definitive causal proof. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261299499, identifier CRD420261299499.
Primary Source
Frontiers in endocrinology
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