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

TL;DR

This review explores how GLP-1 receptor agonists may reduce the risk of liver cancer in people with type 2 diabetes.

Contribution

This is the first scoping review to systematically map the literature on GLP-1RA use and hepatocellular carcinoma risk in type 2 diabetes.

Findings

Six studies showed a significantly reduced risk of HCC with GLP-1RA therapy compared to insulin or sulfonylureas.

GLP-1RA monotherapy was more protective against HCC than combination therapy with insulin.

The protective effect is likely due to anti-inflammatory, metabolic, and immunomodulatory actions of GLP-1RAs.

Abstract

Type 2 diabetes mellitus (T2DM) is a global health burden associated with an increased risk of severe complications, including hepatocellular carcinoma (HCC). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained prominence in the management of T2DM due to their glucose-lowering and weight-reduction effects. Emerging evidence further suggests that GLP-1RAs may mitigate liver-related conditions such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, both of which are major risk factors for HCC development. This scoping review aimed to summarize and map the existing evidence on the impact of GLP-1RA therapy on the risk and management of HCC in adults with T2DM. A comprehensive, systematized search was conducted across EMBASE, Ovid MEDLINE, and Web of Science using terms related to “GLP-1 receptor agonists,” “type 2 diabetes mellitus,” and “hepatocellular carcinoma.” Eligible studies included adult populations (≥18 years) with T2DM prescribed GLP-1RAs and reported outcomes specific to HCC incidence or progression. Six studies met the inclusion criteria, and most demonstrated a significantly reduced risk of HCC among patients with T2DM treated with GLP-1RAs compared with those using insulin or sulfonylureas. GLP-1RA monotherapy was generally more protective than combination therapy with insulin, whereas comparisons with metformin were inconclusive. The observed reduction in HCC risk is likely attributable to the anti-inflammatory, metabolic, and immunomodulatory effects of GLP-1RAs. Current evidence suggests that GLP-1RAs may play a protective role in reducing HCC risk among individuals with T2DM, particularly when compared with insulin-based regimens. Further longitudinal and randomized controlled trials are needed to elucidate the causal mechanisms and quantify the potential role of GLP-1RAs in reducing hepatocarcinogenesis. To our knowledge, this is the first scoping review to systematically map the literature examining GLP-1RA use and HCC risk in populations with T2DM.

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