A popular obesity drug has been found to restore the function of immune cells that target cancer, regardless of whether people lost weight with the treatment.

A small trial led by a team of Irish researchers investigated whether semaglutide, a drug used to treat type 2 diabetes, could also help ease problems with cellular metabolism in people with obesity which may explain their higher rates of cancer and infections.

Weight loss was only ever an unexpected side effect of the drug, which diabetic patients use to keep their blood sugar levels in check. It works by imitating a gut hormone called GLP1, which makes users feel fuller for longer, reducing appetite.

Now it seems semaglutide has another potentially beneficial effect in people with obesity: restoring the function of immune cells called natural killer cells that lead the charge against cancer and infections.

"We are finally reaching the point where medical treatments for the disease of obesity are being shown to prevent the complications of having obesity," says endocrinologist and co-author Donal O'Shea of University College Dublin.

"The current findings represent very positive news for people living with obesity on GLP-1 therapy and suggest the benefits of this family of treatments may extend to a reduction in cancer risk."

That's a long bow to draw from a small study of 20 people, but it is plausible that restoring natural killer cells to their full fighting power could help tamp down cancer risk. We just haven't seen that yet.

Natural killer cells are part of the body's innate immune system, the first line of defense that launches into action at the initial whiff of an intruder. They are known to zero in on cancerous cells and fight infections.

But people with obesity show marked dysfunction in their immune systems, which might be linked to the fact they are also prone to developing other chronic diseases, such as type 2 diabetes, cardiovascular disease, and many types of cancer. They are also susceptible to worse outcomes if they contract infections such as influenza and COVID-19.

Given the overlap between diabetes and obesity, O'Shea and colleagues were interested to see if repurposing semaglutide for the latter could help correct some of the immune imbalance seen in obesity.

The study recruited 20 obese people without diabetes who were about to commence once-weekly semaglutide therapy to manage their weight and looked at samples of their circulating immune cells after six months of treatment.

In a series of lab-based examinations, the researchers found the participants' natural killer cells were no longer in slumps and had begun producing the signaling molecules they normally should, called cytokines. The overall number of natural killer cells in the patients' blood samples had not changed compared to baseline, but their function was restored.

Without a control group, we don't know how this compares to people without obesity if they were to use semaglutide or to people with obesity given a placebo. But it's a good starting point for more research exploring how existing drugs may help address some of the comorbidities of obesity.

The researchers are particularly interested in understanding how cell metabolism underpins immune dysfunction in obesity, as it seems to regulate natural killer cell activity – and could tie this whole story together.

"Cellular metabolism is a critical requirement for natural killer cell functionality, and it can dictate the magnitude of responses," O'Shea and colleagues write in their published paper. "On activation, natural killer cells are shaped and instructed by intrinsic metabolic processes and nutrient availability."

The other interesting thing is that only roughly half of the study participants lost weight on semaglutide, which suggests its restorative effects on immune cells might be irrespective of weight loss.

However, weight loss is what semaglutide is mainly known for. Earlier this year, a surge in popularity among celebrities fuelled global shortages of semaglutide, which is marketed in the US under the name Ozempic. Diabetic patients were scrambling to find their weekly medication to keep their blood sugars from spiking to dangerous levels.

"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," says senior Andrew Hogan, an immunologist at Maynooth University in Ireland.

The study was published in Obesity.