Study links metformin to slowed cognitive decline

Used by millions of people across the globe to optimise blood glucose levels, metformin is regarded as the first-line treatment for most cases of type 2 diabetes.

A six-year study of older Australians with type 2 diabetes has revealed that those taking metformin experienced slower cognitive decline with lower dementia rates than those who did not use the medication.

Led by researchers at the Garvan Institute of Medical Research and the Centre for Healthy Brain Ageing (CHeBA), UNSW Sydney, the study formed part of the Sydney Memory and Ageing Study of 1037 Australians (aged 70 to 90 years old at baseline). The findings are published in the journal Diabetes Care.

“We’ve revealed the promising new potential for a safe and widely used medication, which could be life-changing for patients at risk of dementia and their families,” said first author Professor Katherine Samaras, Leader of the Healthy Ageing Research Theme at the Garvan Institute and endocrinologist at St Vincent’s Hospital Sydney.

“For those with type 2 diabetes, metformin may add something extra to standard glucose lowering in diabetes care: a benefit for cognitive health.”

Protecting brain function

Type 2 diabetes occurs when the body can no longer produce enough insulin to meet its needs, leaving affected individuals unable to maintain blood glucose levels within a normal range. This can lead to long-term health complications, including cognitive decline.

“As they age, people living with type 2 diabetes have a staggering 60% risk of developing dementia, a devastating condition that impacts thinking, behaviour, the ability to perform everyday tasks and the ability to maintain independence. This has immense personal, family, economic and societal impacts,” Professor Samaras said.

The research team investigated data from participants of CHeBA’s Sydney Memory and Ageing Study. In this cohort, 123 study participants had type 2 diabetes, and 67 received metformin to lower blood sugar levels. The researchers tested cognitive function every two years, using detailed assessments that measured cognition over a number of capabilities, including memory, executive function, attention and speed, and language.

The findings revealed that individuals with type 2 diabetes taking metformin had significantly slower cognitive decline and lower dementia risk compared with those not taking metformin. Remarkably, in those with type 2 diabetes taking metformin, there was no difference in the rate of decline in cognitive function over six years compared to those without diabetes.

New use for a common medication

Metformin has been used safely to treat type 2 diabetes for 60 years. It works by reducing the amount of glucose released from the liver into the blood stream and allows the body’s cells to better respond to blood glucose levels.

Studies over the last decade have revealed evidence of metformin’s benefit in cancer, heart disease, polycystic ovary syndrome and weight management. While the current study suggests metformin may have cognitive benefits for people living with type 2 diabetes, the researchers say it may also benefit those at risk of cognitive decline more broadly.

“This study has provided promising initial evidence that metformin may protect against cognitive decline,” Professor Samaras said.

“While type 2 diabetes is thought to increase dementia risk by promoting degenerative pathways in the brain and nerves, these pathways also occur in others at risk of dementia and it is possible insulin resistance may be the mediator.

“To establish a definitive effect, we are now planning a large, randomised controlled trial of metformin in individuals at risk of dementia and [will] assess their cognitive function over three years. This may translate to us being able to repurpose this cheap medication with a robust safety profile to assist in preventing against cognitive decline in older people.”

Senior study author and Co-Director of CHeBA Professor Perminder Sachdev said, “While an observational study does not provide conclusive ‘proof’ that metformin is protective against dementia, it does encourage us to study this and other anti-diabetic treatments for dementia prevention.

“Metformin has even been suggested to be anti-ageing. The intriguing question is whether metformin is helpful ... in those with normal glucose metabolism. More work is clearly needed.”

Image caption: Professor Katherine Samaras. Credit: © Garvin Institute of Medical Research