• Glucagon-like peptide-1 (GLP-1) agonist medications have become increasingly popular over the last year. 
  • Previous  research has revealed both potential positive and negative health  effects when using GLP-1 agonist medications to bind and activate the  GLP-1 receptor.
  • Researchers from Boston  Children’s Hospital have found that blocking, rather than activating,  the GLP-1 receptor triggers the body’s innate defensive immune response  to the development of colorectal cancer via a mouse model. 

Over the last year, a lot of attention has been placed on glucagon-like peptide-1 (GLP-1) agonistTrusted Source medications. 

These medications target a protein called the GLP-1 receptorTrusted Source 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 obesityTrusted Source. Some GLP-1 medications, such as WegovyTrusted Source and ZepboundTrusted Source, 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 healthTrusted Source 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 pancreatitisTrusted Source, depressionTrusted Source, and thyroid cancer. 

Now  researchers from Boston Children’s Hospital have found that blocking,  rather than activating, the GLP-1 receptor triggers the body’s innate  defensive immune response to the development of colorectal cancer via a mouse model. 

This study was recently published in the journal Cell MetabolismTrusted Source. 

GLP-1 receptor can dampen anti-cancer immune response

Previous research has shown GLP-1 may play a role in regulatingTrusted Source the body’s immune system.

Additionally, GLP-1 mRNA expression has been noted in certain types of immune cells, such as T lymphocytesTrusted Source — 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. 

In  the first portion of this study, the researchers discovered that the  GLP-1 receptor acts as a negative costimulatory molecule in T  lymphocytes. 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.

Blocking GLP-1 receptor triggers anti-tumor activity

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.

Blocking the GLP-1 receptor — or GLP-1  receptor antagonism — triggered anti-tumor immune activity in mice with  colorectal cancer, researchers found. 

“While agonism has a  significant immunoregulatory and immunosuppressive function, the  antagonism of [the] GLP-1 receptor is immunostimulatory,” Paolo Fiorina, MD, PhD,  research associate in the Department of Pediatrics Research in the  Division of Nephrology Research at Boston Children’s Hospital and senior  author of this study explained to Medical News Today.

“[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,” he added.

“But we also demonstrated that by blocking the receptor we stimulate the immune system to destroy cancer,” said Fiorina.

What does this mean for GLP-1 receptor agonist drugs like Wegovy? 

As the popular GLP-1 receptor agonist medications like Ozempic and Wegovy activate — rather than block — the GLP-1 receptor, what might this mean for those taking these drugs? 

After reviewing this study, Anton Bilchik, MD, PhD,  surgical oncologist, chief of medicine, and director of the  Gastrointestinal and Hepatobiliary Program at Providence Saint John’s  Cancer Institute in Santa Monica, CA, not involved in the research, told  MNT this was one of the most provocative, interesting studies  he has seen in a long time simply because there has been an explosion of  interest and use of GLP-1 agonist drugs such as Ozempic and Mounjaro. 

“There’s  been evidence to support the use of these drugs in not only reducing  weight loss but also in reducing the chance of developing cardiovascular  disease,” Bilchik told us. “So to suggest that these drugs that work  through this pathway may have an immune effect that increases the risk  of developing colorectal cancer is, quite frankly, astonishing.”

“What  this study is showing is that blocking the GLP-1 — so GLP-1 antagonist —  reduces the chances of colorectal cancer in a mice model,” he added.  “So what the study is suggesting is that GLP-1 agonists may have an  adverse effect.” 

Bilchik said it is “hugely important” for researchers to continue looking for potential adverse effects of GLP-1 medications. 

“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,” he continued. “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.”