Can GLP-1 Receptor Agonists Influence Tumor Biology? A Preclinical Research Overview

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally designed for use in type 2 diabetes management, have become the subject of preclinical investigations focused on their potential to affect tumor biology. While these compounds—such as liraglutide and semaglutide—are not approved for any oncology-related use, laboratory and animal research has explored whether GLP-1 RA exposure may influence tumor growth characteristics in certain malignancy models, including pancreatic, breast, colon, prostate, and some brain tumor lines.

GLP-1 is an incretin hormone that enhances insulin secretion, suppresses glucagon release, slows gastric emptying, and modulates appetite in physiological contexts. Its receptor, GLP-1R, is found in pancreatic tissues and in some non-pancreatic sites—including certain tumor-derived cell lines. This receptor distribution has led researchers to study how GLP-1R activation might alter pathways relevant to tumor development in controlled experimental systems.

In cell culture and animal models, GLP-1 RAs have been observed to reduce proliferation signals within tumor cells. Proposed mechanisms include downregulation of signaling through PI3K/Akt and MAPK pathways and induction of apoptosis in malignant cells, while not producing comparable effects in normal tissue under similar experimental conditions.

GLP-1 RAs may also exert indirect effects in preclinical tumor microenvironments. Reductions in inflammatory mediators and changes in metabolic signaling—particularly insulin resistance—have been recorded in certain models. In breast and colorectal cancer models, liraglutide exposure was associated with smaller tumor volumes, lower expression of inflammation markers, and shifts in immune cell activity within tumor-adjacent tissue.

A 2021 Scientific Reports study found that liraglutide reduced tumor progression in a murine breast cancer model via increased apoptosis and reduced vascular endothelial growth factor (VEGF) expression, a key driver of angiogenesis. Similarly, work in pancreatic and thyroid cancer models has documented interference with tumor cell metabolism and blood vessel formation.

At present, there is no clinical evidence demonstrating tumor size reduction in humans through GLP-1 RA administration, and such studies have not been conducted for regulatory approval. Observational datasets have not found a significant rise in cancer incidence among GLP-1 RA-exposed patients; in some analyses, risk for certain cancer types, including colon and breast, was lower. However, the absence of controlled trials means any cause-and-effect relationship remains unestablished.

Notably, species-specific findings—such as C-cell hyperplasia and medullary thyroid carcinoma in rodent models—have informed precautionary labeling. These rodent effects have not been confirmed in human epidemiologic studies, but the FDA maintains a boxed warning for GLP-1 RAs regarding thyroid C-cell tumors as a conservative measure.

Current research on GLP-1 RAs and tumor biology is preclinical. The observed mechanisms—reduced proliferation signaling, apoptosis induction, anti-inflammatory modulation, and altered angiogenesis—suggest potential avenues for future investigation. Rigorous, controlled clinical trials would be needed to determine whether these laboratory findings translate into safe and effective strategies in oncology settings.

References

1. Koehler JA, Baggio LL, Lamont BJ, Ali S, Drucker DJ. Glucagon-like peptide-1 receptor activation modulates pancreatic islet tumor proliferation in mice. Endocrinology. 2009;150(12):5565–5574.

2. Liu J, Wang Y, Lin L, et al. Liraglutide suppresses breast cancer cell proliferation via mitochondrial apoptosis pathway. Scientific Reports. 2021;11(1):14092.

3. Tomas E, Habener JF. Insulin-like actions of glucagon-like peptide-1: a dual receptor hypothesis. Trends Endocrinol Metab. 2010;21(2):59–67.

4. Drucker DJ. The cardiovascular biology of glucagon-like peptide-1. Cell Metab. 2016;24(1):15–30.

5. Nauck MA, Meier JJ. Incretin hormones: their role in health and disease. Diabetes Obes Metab. 2018;20(Suppl 1):5–21.

6. Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 2011;141(1):150–156.

7. Cucinotta D, et al. GLP-1 receptor agonists and cancer: current evidence and safety profile. Frontiers in Endocrinology. 2023;14:1097214.

Disclaimer

This summary is provided for educational and informational purposes only and reflects findings from preclinical research. GLP-1 receptor agonists are not approved for the prevention, diagnosis, or treatment of cancer. All compounds discussed are intended for research use only. No conclusions should be drawn about their safety or effectiveness in humans.