Scoping review examines GLP-1 drugs' complex relationship with liver cancer: potential protection and risk signals | Research

The takeaway

Scoping review synthesizes conflicting evidence on GLP-1RAs and hepatocellular carcinoma in T2DM: preclinical anti-tumor mechanisms, observational protection signals, but also a recent large study showing modest HCC risk increase—calling for careful risk-benefit evaluation.

Contradictory HCC evidence
GLP-1 drugs show anti-tumor mechanisms preclinically but some observational data suggests modest HCC risk increase—a paradox requiring resolution for millions of users

What the researchers found

Preclinical: anti-tumor mechanisms (anti-inflammatory, anti-NAFLD, anti-proliferative). Some observational: protective signals. Large VA study: 31% HCC risk increase. Contradictory evidence. Need: longer-term studies. T2DM context.

Why it matters

With millions taking GLP-1 drugs, clarifying the HCC risk-benefit is critical. The contradictory evidence means clinicians must currently weigh potential liver protection against potential risk signals.

How the study worked

Scoping review of GLP-1RA effects on HCC risk and management in T2DM.

What this study cannot tell us

Scoping review. Contradictory evidence not resolved. Preclinical ≠ clinical. Observational studies have confounding. No long-term dedicated HCC studies.

How to read the evidence

Scoping review navigating contradictory evidence.

When this study was published

Published in 2025.

The bigger picture

The GLP-1-HCC relationship may be time-dependent: short-term metabolic improvement could reduce HCC risk, while other mechanisms might increase it with prolonged use. Resolving this paradox is crucial.

Questions still open

Does GLP-1 timing (prevention vs treatment) determine HCC direction?
Are specific GLP-1 drugs safer for HCC-risk patients?
Should patients with MASLD cirrhosis avoid or receive GLP-1 drugs?

Common questions

Do GLP-1 drugs protect or harm the liver regarding cancer?

The evidence is contradictory. Laboratory studies show GLP-1 drugs have anti-cancer properties and improve fatty liver disease (which causes liver cancer). However, a large clinical study found a small increase in liver cancer risk with longer GLP-1 use. The truth may depend on disease stage and treatment duration.

Should I worry about liver cancer on GLP-1 drugs?

The overall benefit-risk is likely favorable for most patients. GLP-1 drugs improve many liver disease risk factors. However, patients with pre-existing liver disease should have regular monitoring. The modest risk signal needs larger, longer studies to determine if it is real or due to other factors.

Read the original research

Impact of Glucagon-Like Peptide-1 Agonists on Hepatocellular Carcinoma Risk and Management in Type 2 Diabetes Mellitus: A Scoping Review.

Cureus, 17(12), e100252

View on PubMed ↗Publisher’s paper ↗

Citation

Tungekar, Bassam; Echevarria Cruz, Evelyn C; Dodrill, Jason; Muneeb, Abdul; Sanderfoot, Rachel; Thaj, Omar; Vaishnav, Jeet; Vahidi, Arash; Hindi, Fadi; Khan, Rayyan; Nagy, Stephanie; Jacobs, Robin J. (2025). Impact of Glucagon-Like Peptide-1 Agonists on Hepatocellular Carcinoma Risk and Management in Type 2 Diabetes Mellitus: A Scoping Review.. Cureus, 17(12), e100252. https://doi.org/10.7759/cureus.100252