How Do GLP-1 Agents Factor Into Neuroendocrine Tumor Care Strategies?

As part of the 2025 NANETS Multidisciplinary NET Medical Symposium, CancerNetwork® sat down with Joseph Dillon, MB, BCh, BAO, to discuss his presentation focused on the current uses and risks associated with GLP-1 receptor agonists for patients who are undergoing treatment for neuroendocrine tumors (NETs). Specifically, Dillon highlighted strategies that an oncology team can implement to monitor patients who may initiate GLP-1 agents during their treatment course.

According to Dillon, professor of Internal Medicine-Endocrinology and Metabolism and director of the Neuroendocrine Tumor Clinic at University of Iowa Health Care, certain patients—such as those with NETs located in the thyroid or a history of the genetic disorder MEN type 2—should avoid initiating GLP-1 agents due to risks such as hypoglycemia and gastrointestinal toxicities. He also recommended following up more frequently with patients who initiate GLP-1 agents to ensure no changes in the growth or the symptomatology related to their disease.

Transcript:

Most often, [members of] the oncology team are not the ones initiating a GLP-1 agent because the indication is obesity and diabetes, so these agents are being initiated by their primary care doctors, endocrinologists, etc. Most often, the oncology team are finding that their patients have started on them; sometimes, the patient tells them that their doctor plans to start them on it. Is that okay?

There are some very clear issues. If the patient has a neuroendocrine tumor of the thyroid—that is, a medullary thyroid carcinoma—or a history of the genetic disorder MEN type 2, then they should be strongly counseled not to start those agents because there is a black box on the approval of these agents. In patients with insulinoma, they should not be started on these agents. These agents will stimulate insulin secretion and could cause severe hypoglycemia. It's important for the oncology team to know when patients are starting these agents because many of them have gastrointestinal [adverse] effects, which might be confused with an exacerbation of carcinoid syndrome, which is seen in [patients with] neuroendocrine tumors, which might lead to an increase in the therapy for neuroendocrine tumors, which would not be appropriate.

In people who are starting these agents or taking these agents, it may be necessary to see them at a somewhat more frequent basis, at least over the first 6 to 12 months of taking these agents, to make sure that that there is not a deviation in the growth or the symptomatology associated with the neuroendocrine tumor. The other thing is, at least from the basic research viewpoint, there are tumors that express GLP-1 receptors, particularly pancreatic neuroendocrine tumors and duodenal neuroendocrine tumors, where there's the potential of having growth. There are also neuroendocrine tumors, such as small bowel neuroendocrine tumors and ileal neuroendocrine tumors, which do not, in general, express GLP receptors, for which I would not have a concern with GLP-1 agents.

However, there are newer agents in that marketplace of GLP, which are called GLP-GIP agents, which stimulate both a GLP receptor and a GIP receptor. The GIP receptor is very widely expressed throughout all neuroendocrine tumors, so it may be a matter of suggesting to patients that perhaps they could be on a GLP-1 agent, but they cannot be on a GLP-1/GIP agent. Most famously, those agents would be semaglutide [Ozempic] being a pure GLP agent, whereas tirzepatide [Mounjaro] is a GLP/GIP agent.

Reference

Dillon J. GLP-1 receptor agonists: current clinical uses and potential risks. Presented at the 2025 NANETS Multidisciplinary NET Medical Symposium; October 23-25, 2025; Austin, TX.