Researchers are focusing on strategies to ward off dementia, and they may have found a potential solution in an affordable medication long used for managing diabetes.

Long before Ozempic splashed onto the scene, transforming type 2 diabetes treatment, there was metformin. 

For nearly a century, metformin has been effective in reducing the liver’s glucose production and enhancing the body’s insulin sensitivity. It remains the primary treatment for over 70 percent of newly diagnosed type 2 diabetes patients.

For several years, observational studies have hinted that this staple diabetes medication, which is taken by approximately 19 million individuals at a cost of $2 to $20 monthly, might also offer protective benefits against dementia.

Still, evidence has been mixed, with some studies suggesting the drug exacerbates the development of Alzheimer’s disease, just one type of dementia, and several others saying it has a protective effect on the brain. 

Now, doctors from Taipei Medical University in Taiwan are the latest to make the case for the latter. 

They found that, in half a million overweight and obese people without diabetes, those who took metformin had a lower risk of developing dementia or dying from any cause, regardless of their BMI.

Metformin is the first-line treatment for type 2 diabetes, but the latest research suggested that the drug’s protective effects against dementia in diabetics is more widely applicable to include non-diabetics (stock)

Similar to type 2 diabetes, obesity is a risk factor for dementia. Being severely overweight lowers the body’s defenses against the damage dementia inflicts on the brain and causes chronic inflammation, potentially damaging nerve cells.

Until now, research into metformin as a dementia preventative has primarily focused on people with diabetes. The latest report from Taiwanese researchers is the first to use real-world data to investigate the possibility in people with obesity.

The scientists noted the real-world data reflects a diverse population, making the study’s findings widely applicable. 

They used an electronic health records database covering millions of patients from 66 US healthcare systems, including hospitals, specialty centers, and clinics. 

The researchers said: ‘Since central nervous system inflammation and neuroinflammation are crucial factors in the development and progression of neurodegenerative diseases, the anti-inflammatory and antioxidative effects of metformin are especially beneficial in patients with obesity.

‘Regular, long-term use of metformin may be an efficient way to prevent dementia.’

The study included about 905,000 people in total, split evenly into two groups: those on and those not on metformin. They were matched to be similar in age, health, and other factors for a fair comparison.

The metformin group had been prescribed the drug at least twice in their lives for at least six months. 

The study did not explicitly state why people had been prescribed the drug, but it can be used to treat more than just diabetes, such as prediabetes, those with a metabolic disorder that contributes to obesity, and for polycystic ovary syndrome.

This graph shows the chance of staying free from dementia over time in people with a BMI of 30–34.9. The line with squares represents those taking metformin, while the line with triangles shows those not taking it. Solid lines show the estimated dementia-free rates, and dashed lines show the range where the true rates likely fall

Researchers categorized their study subjects, all adults over 18, into four groups: overweight (BMI 25–29.9), Obese class I (BMI 30–34.9), Obese class II (BMI 35–39.9) and morbidly obese (BMI over 40).

After following patients for 10 years, those who took metformin had a lower risk of developing dementia across all BMI groups. 

The amount of risk reduction varied slightly depending on weight, but two of the groups saw significant results. 

People with a BMI of 30 to 34.9 had a dementia risk about eight percent lower than non-users, while those with a BMI between 25 and 29.9 had a risk about 12.5 percent lower.

People with a BMI of 35 to 39.9 had a four percent lower risk, which researchers deemed statistically insignificant, potentially due to a smaller sample size. 

There was no significant difference in people with a BMI over 40. 

When looking at death from any cause, metformin users also had a significantly lower risk across all BMI categories. 

Metformin’s effect on death risk was stronger than its effect on dementia risk. Those with a BMI between 25 and 29.9 had a 28 percent lower risk of death, while those with a BMI of 30 to 34.9 had a 27 percent lower risk. 

People with a BMI of 35 to 39.9 had a 28 percent lower risk of death, and people with a BMI of 40 or above saw a 26 percent lower risk.  

This graph shows the chance of survival from any cause over time in people with a BMI of 30–34.9. The line with squares represents those taking metformin, and the line with triangles shows those not taking it. Solid lines show the estimated survival rates, and dashed lines show the range where the true rates likely fall

The Taipei team’s findings were published in the journal Diabetes, Obesity and Metabolism. 

Scientists attribute metformin’s recently explored impact on cognitive health and dementia to factors unique to the drug and the condition it treats.

A type 2 diabetes diagnosis is a leading risk factor for dementia, with one sweeping review in 2013 finding that diabetes patients have a 73 percent higher likelihood of developing dementia and a 56 percent higher likelihood of developing Alzheimer’s.

Both conditions affect millions in the US. Around 35 million Americans have type 2 diabetes, while an estimated 7million have dementia, including roughly four to 6 million with Alzheimer’s disease. 

Several studies have resulted in compelling evidence that supports metformin’s anti-dementia abilities. 

In 2020, Australian researchers followed over 1,000 dementia-free seniors aged 70 to 90 from Sydney for up to six years, testing their memory and thinking skills at two and six years.

The study looked at three main groups: people with type 2 diabetes who were taking metformin, those with diabetes who were not, and people without diabetes.

The participants in the study, who did not have dementia at the start, were tested at two years and again at six years for their in-depth memory and executive functioning.

The above graph shows the estimated projection of Alzheimer’s disease patients in the US through 2060

After accounting for other health factors, researchers found that the metformin group had an 81 percent lower risk of dementia compared to those with diabetes who weren’t on metformin.

People with diabetes who didn’t take metformin were nearly three times more likely to develop dementia than people without diabetes.

Brain scans and thinking tests also suggested that metformin users experienced a slower decline in cognitive abilities, particularly in decision-making and overall brain function.