Diabetes research and clinical practiceAug 13, 2025

GLP-1 receptor drugs and the risk of liver cancer and death in people with fatty liver disease and type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 19, 2026

Abstract

GLP-1 receptor agonist use is associated with a 64% lower risk of developing hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus.

Use of GLP-1 receptor agonists was linked to a reduced risk of hepatocellular carcinoma (HCC) in a retrospective cohort study.
The study included 152,329 patients diagnosed with both metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus.
GLP-1 receptor agonist use was also associated with a significant reduction in all-cause mortality.
Adjusted hazard ratios indicated a 0.64 risk for HCC and a 0.37 risk for all-cause mortality among users compared to non-users.
Robustness of these findings was supported by various subgroup and sensitivity analyses.

Simplified

BACKGROUND: Hepatocellular carcinoma (HCC) is increasingly driven by non-viral causes, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), which commonly coexists with type 2 diabetes mellitus (T2DM). Given the strong link between T2DM and HCC and the lack of approved pharmacologic preventive strategies, agents with dual metabolic and oncologic benefits are urgently needed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated anti-inflammatory, anti-fibrotic, and potential anti-tumor effects.

METHODS: We conducted a multinational retrospective cohort study using the TriNetX global network to evaluate associations between GLP-1RA use and incident HCC in patients with MASLD and T2DM. Adults aged 18-90 years with both conditions were identified between 2005 and 2025. Primary outcome was incident HCC; secondary was all-cause mortality. Adjusted hazard ratios (aHRs) were estimated using Cox models.

RESULTS: After matching, 152,329 patients were included in each group. GLP-1RA use was associated with lower risks of HCC (aHR, 0.64; 95% CI, 0.42-0.98) and all-cause mortality (aHR, 0.37; 95% CI, 0.36-0.38). Subgroup, sensitivity, and control analyses supported the robustness of findings.

CONCLUSIONS: GLP-1RA use was associated with significantly reduced risks of HCC and death in patients with MASLD and T2DM, supporting its potential for HCC chemoprevention.

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Competing interests

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

GLP-1 receptor drugs and the risk of liver cancer and death in people with fatty liver disease and type 2 diabetes

Abstract

Full Text

Funding

Competing interests

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