A team of researchers from the University of Iowa has unveiled concerns about the use of semaglutide, a widely prescribed GLP-1 receptor agonist for type 2 diabetes and obesity, in patients with neuroendocrine neoplasms (NENs).
While semaglutide has proven effective in managing blood sugar and promoting weight loss, its effects on certain rare cancer types warrant caution, the researchers note in their in-press article in the journal Surgery. Semaglutide may stimulate the growth of neuroendocrine cancers that express GLP-1 receptors, they found, shedding light on an unanticipated risk for some patients.
The team, led by Po Hien Ear, PhD, measured the expression of GLP-1 receptors and assessed their response to semaglutide treatment in six NEN cell models. The researchers found that three cell lines with high GLP-1 receptor expression showed significant growth when exposed to the drug, with increases of 19% and 22% in two cell models. In mouse models, semaglutide stimulated tumor growth by 72%.
The findings suggest that GLP-1 receptor expression may be a key factor in determining the safety of semaglutide for patients with NENs.
Semaglutide activates pathways that promote cell proliferation, particularly in tumors with high levels of GLP-1 receptors. This raises potential concerns for patients with pancreatic and gastrointestinal neuroendocrine cancer or those with genetic conditions like multiple endocrine neoplasia syndrome (MEN1), which predispose individuals to NENs.
“The impact of semaglutide on neuroendocrine cancer growth is understudied,” says Dr. Ear. “These results indicate a potential risk in the use of semaglutide in patients with NENs expressing GLP-1 receptors. Investigations into a larger set of neuroendocrine neoplasms would be important because they are highly heterogeneous.”
While semaglutide has been shown to reduce the risk of cancer in obese or diabetic patients by alleviating inflammation, these studies involved cancers that do not express GLP-1 receptors. This highlights the importance of tumor-specific research, as the drug’s benefits in one context may pose risks in another. The researchers caution that while semaglutide remains a valuable tool for diabetes and obesity management, its use in patients with GLP-1 receptor-positive tumors should be carefully evaluated.
This study represents a critical step in understanding the complex biology of neuroendocrine tumors and the unintended effects of medications on rare cancers. Future research will investigate the impact of semaglutide on a broader range of neuroendocrine tumor models, including three-dimensional patient-derived tumor cultures.
Based on the results of the study, Dr. Ear and her colleagues encourage patients with neuroendocrine cancer to talk with their doctors before using a GLP-1 receptor agonist.