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Not enough known about GLP-1 agonists, research suggests

There is a gap in scientific knowledge about the type 2 diabetes drugs GLP-1 agonists, according to new research.
The study, which was conducted by researchers from the University of Cambridge and the University of Warwick, concludes that there is a lack of comprehensive information about the impact of GLP-1 receptors.
The study does not suggest that people taking GLP-1 agonists should be concerned. GLP-1 agonists have clear and well-established benefits for people with type 2 diabetes. The study simply suggests that more information would be valuable.
GLP-1 agonists are injectable drugs for people with type 2 diabetes, usually prescribed when dietary changes, exercise, and tablet medication have been unable to bring blood glucose levels under control.
GLP-1 agonists work by stimulating the release of insulin and inhibiting the production of glucagon, the hormone that releases sugar from the liver and into the bloodstream, thereby spiking blood glucose levels. Recent research indicates that GLP-1 agonists also accelerate weight loss.
“What we have shown is that we need a more complete understanding of how anti-diabetic drugs interact with receptors in different parts of our bodies,” said Dr. Graham Ladds of St. John’s College, University of Cambridge.
“GLP-1 agonists clearly benefit many patients with type 2 diabetes and there is no reason to presume that our findings outweigh those benefits. Nevertheless, we clearly lack a full picture of their potential impact. Understanding that picture, and being able to consider all the components of target cells for such treatments, is vital if we want to design drugs that have therapeutic benefits for diabetes patients, without any unwanted side effects.”
This study found that, in certain situations, it might be possible for GLP-1 to bind to the glucagon receptor. In other words, it is possible for GLP-1 to trigger raised blood glucose levels. The researchers found that GLP-1 agonists, which mimic the effects of GLP-1, can have a similar effect.
The researchers found that a protein called RAMP2 prevented GLP-1 from raising blood glucose levels. When RAMP2 was absent, GLP-1 could have this undesired effects. Little is known about RAMP2, but it is understood that it is found in different quantities in different parts of the body.
“The work shows that, contrary to our previous assumptions, glucagon receptors can potentially be activated by anti-diabetic treatments,” said Dr. Ladds.
“To date, very little work has been done on RAMPs, but they clearly play an important part in the process of regulating blood sugar, which is core to helping people with diabetes. The study shows that there is critical need to take this into account when designing new therapeutics.”
The researchers stressed that the findings were preliminary. Further studies are necessary to clarify the potential effects of GLP-1 agonists.
The findings were published in The Journal of Biological Chemistry.

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