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GLP-1 Analogues May Restore Cancer Defences in Obese People

Long-acting glucagon-like peptide-1 (GLP-1) analogues may restore natural killer (NK) cell function in people with obesity, aiding their ability to fight off cancers, according to a new study from Ireland.

Previous research had demonstrated that the recognised higher risk of cancer associated with obesity was in part due to NK cell inactivation. "GLP-1 analogues can actually restore the NK cell function in the body, including its ability to kill cancerous cells," the authors of the new study said. 

GLP-1 analogues, also known as incretin mimetics, act to reduce hunger and thus lower overall calorie intake. They are an effective treatment for obesity, said the researchers, from the Kathleen Londsdale Human Health Institute at Maynooth University, the National University of Ireland in County Kildare.

Obese individuals have "functionally defective NK cells, with a decreased capacity to produce cytokines and kill target cells, underpinned by defective cellular metabolism", they explained. It was plausible, they said, that the changes in peripheral NK cell activity contribute to the multimorbidity of obesity, which includes an increased risk of cancer.

Semaglutide Restored NK Cell Function

The researchers set out to investigate whether GLP-1 analogues might also restore NK cell functionality and metabolism in people with obesity. They assessed 20 obese patients receiving once-weekly GLP-1 therapy with semaglutide for 6 months, using multicolour flow cytometry, enzyme-linked immunosorbent assays, and cytotoxicity assays.

The study's results, published in Obesity, showed that semaglutide improved NK cell function, as measured by cytotoxicity and interferon-γ/granzyme B production. In addition, the results showed increases in a CD98-mTOR-glycolysis metabolic axis, which is critical for NK cell cytokine production. 

The restored cancer-killing effect of NK cells was independent of the GLP-1's main weight loss function, the team said, "so it appears the treatment is directly kick-starting the NK cells' engine". They concluded that their findings "showcase" the drug's ability to restore the body's natural cancer-killing defences.

'Tangible Benefits' in Addition to Weight Loss

Corresponding author and principal investigator Andrew Hogan, associate professor at Maynooth University, said: "My team and I are very excited by these new findings in relation to the effects of the GLP-1 treatment on people with obesity, and it appears to result in real tangible benefits for those currently on the drug."

Conor de Barra, a PhD student in immunology at Maynooth University, who led the work in Dr Hogan's lab, said: "People with obesity can develop a variety of health problems like type 2 diabetes, sleep apnoea, and cancer. These can have very negative impacts on their quality of life. This research and other promising findings on improvements in cardiovascular health after GLP-1 therapy indicate its potential benefits in addition to weight-loss."

Co-principal investigator Professor Donal O'Shea, from the Obesity and Immunology Research Group at Maynooth, said: "We are finally reaching the point where medical treatments for the disease of obesity are being shown to prevent the complications of having obesity. 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."

Some GLP-1 drugs, which include currently trending weight loss drug semaglutide (Wegovy), are available on the NHS through specialist weight management services for people with severe obesity not responding to other approaches. They must be given by injection.

Drug's Popularity has Created Shortage

Dr Hogan added: "While these findings will understandably be welcomed by those living with obesity and looking for safe and effective treatments, given the recent spike in popularity related to the benefits of the GLP-1 treatment with global and high-profile celebrities commenting on its success, global demand has increased and resulted in a worldwide shortage of the drug.

"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."

Dr Hogan will present these findings at the 30th European Congress on Obesity, which will be held in Dublin on 20th of May.

This study is supported by the Health Research Board. Conor De Barra is supported by a fellowship from Irish Research Council. Financial support for the Attune NxT was provided to Maynooth University Department of Biology by Science Foundation Ireland. The authors declared no conflict of interest.