Metformin and Dementia: What’s the Connection?

Key Takeaways

Some observational studies suggest that metformin therapy is associated with a decreased dementia risk in people with type 2 diabetes, but the results are mixed and inconsistent.
One study found that the risk of developing dementia is 21% higher in people who are prescribed metformin but stopped using it compared to those who continue taking metformin.
Another diabetes medication, pioglitazone (Actos), may offer protection against dementia in older adults with a new diagnosis of Type 2 diabetes mellitus and a history of cardiovascular disease such as stroke or ischemic heart disease.

Metformin is a diabetes medication that is prescribed to people with Type 2 diabetes mellitus. It is used alone or with other medications to achieve more intensive blood glucose control for those who need extra help to get to their goal of blood glucose and hemoglobin A1c (HbA1c).

Metformin acts by reducing glucose production in the liver and lowering insulin resistance. However, the insulin sensitizer metformin can also affect dementia risk. Please keep reading to find out the association between metformin use and dementia.

Is there a correlation between metformin and dementia?

Some studies have found that metformin usage can reduce the risk of dementia, while others have found metformin increases the risk of Alzheimer’s disease, a common type of dementia.

Metformin can reduce dementia risk

Metformin treats type 2 diabetes mellitus and insulin resistance, which are known risk factors for dementia and chronic conditions like cerebrovascular disease.

Studies have shown that people who took the antidiabetic drug metformin had a significantly lower risk of dementia compared to people without metformin exposure or exposure to other antidiabetic medications. People receiving metformin therapy long-term had an even lower dementia risk.

Other studies have found that people receiving metformin at low doses had a lower risk of dementia. However, higher doses of metformin did not protect against dementia.

Research has also shown that people with normal kidney function who stopped metformin treatment had a higher risk of dementia compared to people who continued metformin use.

Metformin can increase the risk of Alzheimer’s disease

While there is some evidence linking metformin use to a reduced risk of dementia, there is also evidence linking metformin use to an increased risk of Alzheimer disease.

Studies have found metformin use significantly increased Alzheimer’s dementia incidence. The risk of developing dementia was higher with higher doses of metformin and in people with a longer duration of diabetes mellitus. Also, the metformin-associated increase in Alzheimer’s disease risk was significantly more in people with depression.

In addition, studies in mice have shown that metformin promotes tau aggregation, which is an abnormal neurological finding in Alzheimer’s disease.

What is the verdict?

The research that investigates the benefit of metformin in reducing the risk of developing dementia has been observationally studied, meaning it was designed to discover a trend but not meant to establish metformin’s role in improving cognitive function.

However, what we do know is that Type 2 diabetes is a risk factor for developing cognitive problems such as dementia. Interestingly, studies found that insulin plays a role in clearing amyloid-beta peptide and tau phosphorylation, hallmarks of Alzheimer’s disease.

Therefore, brain insulin resistance may play a role in cognitive decline in people with Alzheimer’s disease and other types of dementia.

Other facts to keep in mind regarding the association between diabetes and dementia are:

Diabetes, left untreated or uncontrolled, can lead to kidney injury, chronic kidney disease, and high blood pressure, which can lead to stroke and heart attack.
Poorly controlled diabetes can cause very high blood sugar levels and dangerously low blood sugar levels, which can cause dizziness, anxiety, and shakiness.
Perpetually low blood sugar can lead to cognition problems, memory loss, and, eventually, dementia.

With all this being said, while the role of metformin in reducing the risk of dementia needs further studies, there is evidence indicating the association between poorly controlled diabetes and dementia.

Why is metformin not recommended for the elderly?

Metformin may not be recommended for elderly patients (people 65 years of age and older) due to their naturally declining renal function. Therefore, taking metformin can cause kidney injury and chronic kidney disease (CKD).

Can you take metformin if you have a dementia diagnosis?

Your doctor will decide if you can take metformin if you have mild cognitive impairment, severe cognitive dysfunction, or a dementia diagnosis.

Metformin helps to control high blood glucose levels and treat Type 2 diabetes mellitus, which is a risk factor for Alzheimer’s disease and other types of dementia. In addition, metformin increases insulin sensitivity, which is often altered in Alzheimer’s and dementia patients.

Some observational studies suggest that metformin therapy is associated with a decreased dementia risk in people with Type 2 diabetes. However, randomized controlled clinical trials are necessary to establish the connection further.

Can I take metformin to enhance cognitive performance?

Metformin is FDA-approved to treat Type 2 diabetes. Clinical trials have not confirmed that a metformin prescription can prevent accelerated cognitive decline or enhance cognitive function in people without diabetes.

Long-term use of metformin can increase the risk of certain health problems, such as vitamin B12 deficiency and kidney injury.

Therefore, metformin prescriptions are not recommended in non-diabetic individuals to enhance cognitive performance or prevent cognitive impairment.

Which diabetes drug may lower risk of dementia?

In addition to metformin, another diabetes medication, pioglitazone (Actos), may offer protection against dementia in older adults with a new diagnosis of Type 2 diabetes mellitus and a history of cardiovascular disease, such as stroke or ischemic heart disease.

The bottom line

While further research is necessary to learn about the role of metformin in preventing the development of dementia, it is important that you take this medication as directed.

Compliance is essential to manage your blood sugar levels and prevent other health complications such as kidney disease and cardiovascular problems.

Poorly controlled diabetes with very high or very low blood glucose levels can negatively impact cognitive function. Therefore, keeping your diabetes under control helps reduce the risk of memory loss and dementia.

Talk to your doctor if you can’t tolerate metformin due to the pill size or texture or if the gastrointestinal side effects of metformin affect your compliance with this medication.

Metformin is also available as an oral suspension, which can help with swallowing.

Metformin extended-release formulation is less likely to cause unpleasant side effects such as nausea, vomiting, and diarrhea.

Your doctor will help you determine a diabetes treatment regimen that works best for you. If metformin is not a good option for you, there are metformin alternatives available.

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