Making Sense of GLP-1 RAs During Cancer Care: Insights from Oncology Pharmacists

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming increasingly common in clinical practice, but their role in oncology—especially alongside immunotherapy and treatments for head and neck cancers—remains complex. In this conversation, oncology pharmacists Colleen McCabe, PharmD, BCOP, and Lindsay Mundy, PharmD, discuss how they evaluate risks, weigh patient motivations, navigate nutritional challenges, and apply emerging evidence to real-world decision-making. Their insights offer practical frameworks for pharmacists facing similar questions in their own practice.

Q:Melanoma treatment increasingly relies on immunotherapy, which already carries a significant gastrointestinal (GI) toxicity burden. When a patient on a checkpoint inhibitor also wants to stay on a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for weight management, how do you think through that risk-benefit conversation?

Colleen McCabe, PharmD, BCOP: Yeah, so melanoma is a little bit different than chemotherapy. You know, with chemotherapy we have a lot of weight loss, nausea, and issues that could come with that, and we do not see that as much with immunotherapy. So really, the risk with immunotherapy that we are thinking of, of course, is the colitis risk with the GI toxicity that can develop. Usually it is pretty dramatic when patients develop colitis on immunotherapy. It is typically not just a little bit of nausea or one bout of diarrhea—something that we might see with glucagon-like peptide-1 (GLP-1) agents such as semaglutide (Ozempic; Novo Nordisk) or liraglutide (Victoza; Novo Nordisk). It can start that way, but usually it comes on pretty quickly if a patient actually develops it.

So it is a little bit more of a nuanced conversation with them, and it is not as explicit as “these are overlapping toxicities,” because the mechanisms of action behind them are very different. And the way that we would treat, say, GI toxicity from a GLP-1 agent versus immunotherapy is very different. So it is really, again, just making sure that the patient is aware of what the side effects from each of those would look like, and also realizing what their health literacy is as far as being able to differentiate those symptoms at home.

Q:Patients with head and neck cancers often face profound nutritional challenges, and GLP-1 RAs can suppress appetite and slow gastric emptying. How do you think about using or continuing these agents in that context, where maintaining nutritional status is already a battle?

Lindsay Mundy, PharmD: Yeah, absolutely. And again, it kind of goes back to our initial conversation. When I am evaluating those patients, unless there is a very extreme reason that we have to keep them on—especially for our concurrent chemoradiation—my team is very quick to pull that drug during their treatment.

Now, if we are talking more about recurrent or metastatic disease, with somebody who is maybe on more of a palliative treatment, I do not anticipate that the weight loss and some of the nausea and side effects are going to be as extreme with their treatment. But during that concurrent chemoradiation phase, the nutritional deficiencies, the extreme weight loss, and just managing nausea and vomiting—especially if we are having to switch them over to tube feeds or something along those lines—it is just not really worth the risk unless, again, there is an extreme medical reason, like extremely uncontrolled diabetes or something along those lines.

But generally, there are enough antidiabetic medications out there that we can find a regimen that will work for them and will hopefully help eliminate some of those GLP-1 side effects.

Q:Head and neck cancers have a strong association with human papillomavirus (HPV) and with tobacco and alcohol use. Is there a patient profile where you would see a genuine clinical case for GLP-1 RA use alongside active treatment, and what would that look like?

Mundy: Yeah, so I would love to have that data. I think some of the retrospective information that we will be covering in our talk is looking at teasing out some of the obesity-associated cancers and what the benefit and risk is within each of those disease subsets. Head and neck cancer, again, does not really have an obesity-associated factor with the cancer risk. It is more of these other risk factors, so I do not anticipate that would have a large impact.

Although, we have also seen that GLP-1 receptors are all over the body, and even when you are looking at the cardioprotective, renoprotective, maybe even neuroprotective effects of these agents, it would not surprise me if there is something that we just still do not know about how these are interacting with different systems in the body.

McCabe: Yeah, and one point that Lindsay makes that I really like is that even if it is just a small percentage that we see in the patient population of risk reduction, that can still have a huge impact on cancer cases overall. Even if it seems like a small percentage, we are talking about a lot of patients nationally.

Q:Attendees are going to leave your session with practical frameworks, but the evidence base here is still evolving quickly. What is the one thing you hope oncology pharmacists take away from this session—not just about GLP-1 RAs but about how to approach emerging, controversial topics like this in their own practice?

McCabe: Yes, I think the biggest thing that I hope people take away from this session is just how to open up these lines of communication with the patient to try to understand their motivations or understand all the different factors that are coming into this decision. I think it is easy as pharmacists—we really like to follow the evidence, follow the guidelines. But as you can see, everything is ever-evolving. We have more and more controversial therapies coming to market and becoming popular. So it is about how to have those thoughtful lines of communication with patients so that you are getting the full picture and therefore can help them make the best decisions.

Mundy: Yeah, and I think sometimes, as oncology pharmacists, we want to be focused so much on what our treatments are—so what is our chemotherapy, what is our immunotherapy, or what that is. And I do not want to say we want to be siloed, but sometimes we think, “Those are diabetes medications; carry on.”

But I think it is important to look at some of the literature that is coming out, especially when we think about some of our oral chemotherapies with GLP-1 agents delaying gastric emptying. As we talked about, decreasing absorption—could this have an impact on our oral chemotherapy agents as well, and how are we going to help navigate that?

I think oncologists are really poised to be in a great position to help alleviate some of that. Think through: What are other medical options for the patient? And then how do we have those discussions with patients or even with interdepartmental teams to make sure that we have the best medication regimen for the patient?

McCabe: Yeah, that actually just spurred a thought. We had a conversation earlier about how we have now seen the long-term effects of bariatric surgery and the impact that has had on our ability to treat patients with cancer. And so it was an interesting thought point: Would you rather have a patient with a history of bariatric surgery when trying to treat with chemotherapy, or a patient who has been using a GLP-1 agent? So I think long-term there could be more discussions about what that would look like as well.