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Metformin in the brain: friend or foe?

Project summary

Many people who use metformin to manage their type 2 diabetes, often need to start on a second medication to control blood sugar levels. Dr Beall wants to better understand the effect of metformin in the brain and why this may cause some people with type 2 to stop responding to it over time. He’ll also shed new light on if and how metformin may have anti-inflammatory effects in the brain. In the future this could help us to understand who is more likely to need an add on treatment and open-up new ways to keep the brain healthy in people with diabetes. 

Background to research

Metformin is the most common treatment for type 2 diabetes and is prescribed to millions of people in the UK. Over time, some people with type 2 can stop responding as well to metformin and need to take a second type of diabetes medication to manage their blood sugar levels.  However, we still don’t fully understand why this happens. 

Metformin helps the insulin you produce to work better and reduces the amount of glucose released by the liver. 

Previous research has shown that metformin can also enter the brain. And here it may have the opposite effect to the way it works in the liver, causing blood sugar levels to rise.  

Dr Beall wants to explore exactly how metformin works in the brain and if this is a reason why the drug stops working properly for some people with type 2 diabetes. 

In addition to this possible downside of metformin in the brain, the drug may have positive effects in the brain too, which Dr Beall also wants to unravel. 

Research aims

Dr Beall and his PhD student will study how metformin controls blood sugar levels in the brain. 

Firstly, they’ll ask whether metformin in the brain is a friend? They will grow brain cells in the lab and bathe them with metformin. They’ll investigate if metformin can help to limit inflammation in the brain that’s linked to frequent high and low blood sugar levels.

Next the researchers will ask if metformin in the brain is a foe? Rats with type 2 diabetes will be treated with metformin and a new drug that activates the brain’s ‘fuel gauge’. They’ll explore how the brain, liver, muscle and pancreas interact when the mice are given these medications. This will allow them to pinpoint if increases in metformin in the brain reduces the glucose lowering effect of metformin in in the liver.  

Finally, Dr Beall and his PhD student will examine newly discovered insulin-producing brain cells and investigate if these contribute to blood sugar control.

Potential benefit to people with diabetes

Approximately 1 in 6 people with type 2 diabetes who take metformin will need a second medication within a year. Within 5 years, around 1 in 2 people will be taking an additional drug. This research could help shed new light on who these people are and why this happens. 

New insights into possible beneficial effects of metformin on brain health could also give us ways to better protect the brain health of people with diabetes and help us understand the potential of metformin as a new dementia treatment.  

Finally, learning more about insulin that’s made in the brain may in the future open doors to harness this newly discovered sources of insulin, to treat all types of diabetes.  

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