Our researchers have uncovered new insights into how our genes can affect how well type 2 diabetes treatments work.
The findings from Dr Tomas and her PhD student at Imperial College London could help pave the way for more personalised type 2 treatments in the future.
Dr Tomas and her student focused on a gene called GLP1R, which helps control blood sugar levels.
The GLP1R gene makes a tiny protein on the surface of insulin-producing beta cells called the GLP-1 receptor. This receptor tells beta cells to release insulin, helping to bring down blood sugar levels.
Treatments called GLP-1 agonists, like semaglutide, activate the GLP-1 receptor. These drugs are used to treat type 2 diabetes and obesity. But people respond to them very differently.
Scientists have already discovered that people who have a change in their GLP1R gene have a lower risk of developing type 2 diabetes – and its complication coronary heart disease – than people without the change. This is because the altered receptor is better able to lower blood sugar levels.
We funded Dr Tomas and her student to investigate how exactly this happens.
They compared mice with type 2 diabetes with and without the change in their GLP1R gene.
What did the researchers find?
The team showed that mice with the GLP1R gene change had better-performing beta cells. Their beta cells more effectively produced insulin, leading to improved blood sugar control. These mice also gained weight more slowly than mice without the gene change.
They also uncovered how the gene change affected the structure of the GLP-1 receptor it makes, using extremely high-resolution microscopes. This likely explained why these effects happened - shedding light on why the protein may help protect against type 2 diabetes.
But they also found that mice with the GLP1R gene change did not respond as well to GLP-1-targeting treatments, like semaglutide.
What does this mean?
This is early-stage research, but the findings may help explain why some people benefit less from certain type 2 diabetes medications. In the future, this could support personalised treatment for type 2 – where doctors choose treatments based on a person’s individual characteristics, like their genes.
The results could also inform the development of new GLP-1 based drugs, designed to work more like the naturally altered GLP-1 receptor, improving treatment for more people.
Dr Tomas said:
“Our findings are important because they show that genetics can influence both type 2 diabetes risk and response to treatment. In the future, our discoveries could lead to personalised treatments for type 2 diabetes and obesity, tailored to a person’s genetic makeup.”
What’s next?
This study also opens the door to pinpointing other genetic changes that affect GLP-1 receptors and type 2 diabetes risk.
The research has now been accepted for publication in the journal Science Advances.
Find out more about this research.
