Influence of glucagon‐like peptide‐1 receptor agonists on hepatic events in type 2 diabetes: a systematic review and meta‐analysis

Sep 25, 2024Journal of gastroenterology and hepatology

Glucagon-like peptide-1 receptor agonists and liver problems in type 2 diabetes: a review and combined analysis

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Abstract

GLP-1 receptor agonist use is associated with a 74% reduced risk of hepatocellular carcinoma in type 2 diabetes patients.

Approximately 69% of type 2 diabetes patients have metabolic dysfunction-associated steatotic liver disease.
Use of GLP-1 receptor agonists is linked to a 32% reduction in the risk of cirrhosis decompensation.
Significant reductions in variceal bleeding and hepatic encephalopathy were observed among those with cirrhosis decompensation.
No significant differences were found in the prevention of cirrhosis or hepatic failure.
A positive correlation exists between the incidence of hepatocellular carcinoma and both male sex and longer follow-up duration.

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BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM) is intrinsically linked to various etiologies of liver disease, with 69% of patients having concomitant metabolic dysfunction-associated steatotic liver disease (MASLD). Studies suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorating liver disease. With this analysis, we address the gap in knowledge about the effectiveness of these agents in preventing different major adverse liver outcomes (MALOs).

METHODS: PubMed, Embase, and The Cochrane Central of Trials were searched for articles reporting MALOs in T2DM patients. Publication bias-identifying methods, quality assessment and sensitivity analyses (subgroup analyses, leave-one-out meta-analyses, and meta-regression) were employed. Statistical analyses were performed in R using the "meta" and "metafor" packages.

RESULTS: Nine cohort studies from 535 identified articles encompassing 579 256 T2DM patients were included in the main analyses. GLP-1RA use was associated with reduced risks of hepatocellular carcinoma (HR 0.74, 95% CI 0.56-0.96) and cirrhosis decompensation (HR 0.68, 95% CI 0.65-0.72). Within the latter, variceal bleeding and hepatic encephalopathy prevention were found to be significantly reduced. Egger's test, Begg's test, and funnel-plot analysis yielded no publication bias. No significant differences were observed in preventing cirrhosis or hepatic failure. Meta-regression analysis revealed a positive correlation between hepatocellular carcinoma incidence and both male sex and longer follow-up duration.

CONCLUSIONS: This meta-analysis improves our understanding of the hepatoprotective effects of GLP-1RAs in T2DM patients and supports existing research, exhibiting superiority over other antidiabetic medications for hepatoprotection in this subgroup. Additional long-term follow-up studies are necessary to further validate these findings.

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Influence of glucagon‐like peptide‐1 receptor agonists on hepatic events in type 2 diabetes: a systematic review and meta‐analysis

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