Over the last year, a lot of attention has been placed on glucagon-like peptide-1 (GLP-1) agonist medications. These medications target a protein called the GLP-1 receptor, which is located on pancreatic cells, binding to and activating them to help stimulate insulin production and slow food from exiting the stomach.
GLP-1 agonists were originally approved for use to treat type 2 diabetes. Currently, some GLP-1 agonists are being used off-label for treating obesity. Some GLP-1 medications, such as Wegovy and Zepbound, have also received Food and Drug Administration (FDA) approval for weight management in adults with obesity.
Some recent studies have reported other potential positive effects of GLP-1 medications, including improved cardiovascular health and protection against kidney disease.
On the flip side, other research found GLP-1 medications may be linked to negative effects including an increased risk for pancreatitis, depression, and thyroid cancer. Previous research has shown GLP-1 may play a role in regulating the body’s immune system.
Additionally, GLP-1 mRNA expression has been noted in certain types of immune cells, such as T lymphocytes — a type of white blood cell that helps the body fight off germs and diseases. A process called costimulation — a secondary signal that immune cells need to activate an immune response — is vital for T lymphocytes to work correctly. When T cells receive negative costimulatory signals, their activity is suppressed. If T cells do not receive positive costimulatory signals, they may become anergic. This means they are inactive and do not initiate an immune response to an antigen, such as those on viruses or bacteria. From there, the scientists used a mouse model to discover that the GLP-1 receptor acts as a checkpoint molecule, curbing the immune system’s response to cancer. The GLP-1 receptor is not acting as an enabler of cancer, actually it is the opposite. GLP-1 receptor agonism reduces inflammation in a variety of ways because of its anti-inflammatory and immunoregulatory functions. Researchers also demonstrated that by blocking the receptor we stimulate the immune system to destroy cancer.
Doctors who have reviewed this study say that There is no other type of medication that is being increased more and being utilized more than these GLP-1 agonist drugs, and so far, the recommendations have been expanding in terms of not only treating diabetes and obesity but also reducing the risk of cardiovascular disease. So, the fact there may be adverse effects to the use of these drugs, particularly relating to cancer, is enormously important and warrants further investigation. Some researchers highlight that while prevention of the disease is paramount, a recent international collaboration entitled ‘Glucagon-like peptide 1 receptor is a T cell negative costimulatory molecule’ triggered anti-tumor immunity in a murine model of colon and rectal cancer. Additional research to be considered is if the patient population is obese or not, who develop colon and rectal cancer while taking GLP-1 receptor medications. These individuals may have a different molecular genetic profile affecting the anti-tumor immunity.
