Ozempic and Wegovy have taken over obesity treatment. Can they help with cancer, too?

Novo Nordisk’s Ozempic and Wegovy may have benefits beyond helping patients shed pounds. They appear to reverse the impairments in cancer-fighting natural killer cells seen in people with obesity, independent of weight loss.

In the results of a study published May 9 in the journal Obesity, researchers from Maynooth University in Ireland reported that a long-acting glucagon-like peptide-1 (GLP-1) analogue restored natural killer cell function in 20 people with obesity. While the drug class has previously been associated with lower risks of type 2 diabetes and cardiovascular disease, the finding marks the first time researchers have discovered this particular property of GLP-1 analogues.

"If we can harness GLP-1 receptor agonists to improve immune function and reduce cancer risk, that is very exciting," Katherine Saunders, M.D., obesity medicine physician and co-founder of Intellihealth—a software and clinical services company for medical obesity treatment—told Fierce Biotech research in an email. 

Natural killer cells are a type of white blood cell that kills viruses and cancer cells. They come from the same family of cells as T and B cells, but differ in that they unleash their destructive power without having to be primed or activated first (hence the term “natural” in their name). While natural killer cell activity is actually enhanced in the early stages of obesity, as the cells move into adipose tissue and stimulate inflammation, those in peripheral circulation lose their cytotoxic potency over time if weight gain is persistent. This is believed to be one of the mechanisms that explains why there is a higher incidence of cancer in people with obesity than in those of a lower weight.

The team behind the study had previously looked at how obesity affects natural killer cell metabolism, finding a direct link between obesity-driven defects in natural killer cell activity and poor outcomes in mice with cancer. Their earlier work had also shown that GLP-1—a hormone produced in the intestines and released in response to food—modulates the immune system in a way that’s necessary for weight loss. Studies by other teams had shown that GLP-1 also regulates macrophages, natural killer cells and T cells

To see how GLP-1 agonists affected natural killer cell activity, the researchers first drew blood from non-diabetic patients with obesity to confirm that the cells’ function was impaired. They then gave them a once-weekly dose of semaglutide, the pharmacological name for Ozempic and Wegovy, beginning at the typical starting dose of 0.25 mg and working up to 1 mg over the course of six months. None of the patients had used the drug before.

At the end of the study period, the researchers took blood samples from the patients again to assess natural killer cell activity. They found that while the frequency of the cells didn’t change, their function had improved. The natural killer cells produced greater numbers of cytokines, the inflammatory molecules used to take down invaders or cancerous cells. Further analysis of the blood samples showed that various components of metabolism processes that take place within natural killer cells were restored.

Given that the patients in the study lost weight, it would be reasonable to assume that the weight loss itself was behind the improvements in natural killer cell activity. But mathematical analysis of the findings suggested this wasn’t the case: There was no statistical relationship between weight loss and improvements in the various components of natural killer cell metabolism and cytokine production. Furthermore, taking natural killer cells from people with obesity and treating them directly with GLP-1 in a petri dish showed the same improvements.

Though the study was small and relatively short, Saunders believes it's a great proof-of-concept that could guide further research. 

"These findings are preliminary, but certainly encouraging," she said. "I would love to see more data from future studies."

Ozempic and Wegovy have risen to blockbuster status on account of their ability to help patients lose weight quickly with few short-term side effects. Unpaid celebrity endorsements from the likes of Elon Musk have sent even patients without obesity scrambling to get the drugs, leading to shortages.

In a press release about the findings, lead researcher Andrew Hogan, Ph.D., lamented the lack of access to the drugs.

“I hope this is something that is brought under control to ensure as many people as possible living with obesity can start their own treatment of this beneficial drug,” he said.

Novo Nordisk was not involved in the study. The authors reported no conflicts of interest.