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Glucagon-like peptide-1 receptor agonists and advanced liver outcomes in type 2 diabetes: a systematic review and

Jing-Hong Hu1, Ming-Ling Chang2, Tung-Jung Huang3

  • 1Division of Gastroenterology and Hepatology, Yunlin Chang Gung Memorial Hospital, Yunlin, Taiwan.

Frontiers in Endocrinology
|June 18, 2026
PubMed

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show a promising trend for improving advanced liver outcomes in type 2 diabetes patients. However, this evidence is hypothesis-generating, not definitive proof, due to study limitations.

Area of Science:

  • Metabolic disorders and liver health
  • Pharmacological interventions for diabetes and obesity

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known to improve glycemic control, weight, and cardiometabolic risk factors in type 2 diabetes (T2D).
  • Randomized trials have lacked the power to assess the impact of GLP-1RAs on advanced liver outcomes.

Purpose of the Study:

  • To systematically review and conduct an exploratory meta-analysis of real-world comparative cohort studies on GLP-1RAs and advanced liver outcomes in adults with T2D.
  • To focus on studies with active comparators, advanced liver endpoints, and transparent causal inference limitations.

Main Methods:

  • A systematic review of PubMed/MEDLINE and Embase, including citation chasing and an updated search up to April 25, 2026.
  • Inclusion of 12 comparative real-world cohort studies, with four studies comparing GLP-1RAs to DPP-4 inhibitors for meta-analysis.
  • Exploratory random-effects meta-analysis using Hartung-Knapp and conventional REML methods for incident cirrhosis or composite serious liver events.

Main Results:

  • The pooled hazard ratio (HR) for advanced liver outcomes with GLP-1RAs versus DPP-4 inhibitors was 0.85 (95% CI 0.74-0.98) using the primary method.
  • A secondary analysis yielded a narrower interval (95% CI 0.79-0.93) with no heterogeneity (I²=0%).
  • The certainty of evidence was rated as very low due to the observational nature of studies, varied outcome definitions, and potential biases.

Conclusions:

  • GLP-1RA use demonstrates a directionally favorable signal for advanced liver outcomes in individuals with T2D.
  • The current evidence is considered hypothesis-supporting rather than conclusive proof of a causal relationship.
  • Further research is needed to confirm these findings with higher certainty.
Keywords:
comparative effectiveness researchdiabetes mellitusglucagon-like peptide 1 receptor agonistshepatocellular carcinomaliver cirrhosismetabolic dysfunction-associated steatotic liver diseasereal-world evidencetype 2

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