Dementia: Stopping diabetes drug metformin may increase risk

  • Researchers say the diabetes drug metformin may help decrease the risk of developing dementia.
  • The researchers based their conclusions on their study in which they said people who stopped taking metformin before developing kidney disease had a higher risk of dementia.
  • Experts note that metformin can be effective in treating certain conditions, but the drug also has some serious potential side effects.

People without kidney disease who stopped taking metformin had an increased risk of developing dementia, according to a study conducted at Kaiser Permanente and published today in the journal JAMA Network Open.

In their study, researchers analyzed the health records of 12,220 people who stopped metformin, sold under the brand names Fortamet and Glumetza, before developing kidney dysfunction.

They compared them to 29,126 individuals who continued to take metformin. They then matched participants in both groups by age and gender.

The participants were born before 1955 and did not have a history of kidney disease when enrolled in the study. A review of medical records began when electronic medical records became available (which started in 1996) and continued until age 90, death, a 90-day gap of use of metformin, or a dementia diagnosis.

The scientists looked for an association between stopping metformin and all-cause dementia.

The researchers reported that people who terminated the use of metformin early – before kidney dysfunction – had a 1.21 times higher risk of receiving a dementia diagnosis. The researchers believe this showed that the association was primarily independent of changes in the HbA1c levels and insulin usage.

The scientists suggest that this finding could have potential implications for health in later life and that it might be beneficial to stay on metformin. Decreasing the dosage, switching to a slower-release form, or taking the drug with food in the evening might also help alleviate gastrointestinal problems.

The limitations of this study include:

  • The researchers used medical records to determine dementia diagnosis. As such, the individual might not have sought treatment and the condition could have started at any time before the records review.
  • Researchers did not look at race, ethnicity, or duration of metformin use.
  • The medical records did not include the reason for the termination of metformin.

What to know about dementia

“Dementia is characterized by marked, persistent, and disabling decline in two or more intellectual abilities, such as memory, language, judgment, or abstract reasoning, that significantly interfere with and disrupt your normal daily activities,” said Dr. Verna Porter, a neurologist and director of the dementia as well as the Alzheimer’s Disease and Neurocognitive Disorders unit at Providence Saint John’s Health Center in California who was not involved in the study.

“When memory loss becomes so pervasive that it begins to disrupt your work, hobbies, social activities, and family relationships, this may suggest the warning signs of an evolving dementia syndrome or a condition that mimics dementia,” she explained to Medical News Today.

According to Porter, you should seek out care if you or a family member notices that you are:

  • Repetitively asking the same question.
  • Forgetting a word/phrase or idea when speaking.
  • Inserting the wrong word in conversation, e.g., saying “chair” instead of “sofa,” for example.
  • Taking longer to complete daily chores, tasks, or affairs (e.g., paying bills or managing the mail).
  • Frequently misplacing objects/items around the house.
  • Getting lost while walking or driving in a relatively familiar area.
  • Having sudden or unexplained changes in mood, personality, or behavior without an apparent reason .

What to know about metformin

The Food and Drug Administration has approved metformin to treat type 2 diabetes for people 10 years and older who are not meeting their target blood glucose levels despite following a healthy diet and getting regular exercise, according to Harvard Health.

The drug can also help with other health conditions, such as:

  • Delaying or preventing the onset of diabetes in people with prediabetes
  • Helping with menstrual regulation, fertility, and elevated blood sugar in women with polycystic ovary syndrome
  • Reducing weight gain from antipsychotic drugs

Researchers are also looking into metformin as a way to slow aging as well as reducing stroke risk and cognitive decline.

Porter points out that a few studies show that the use of metformin for type 2 diabetes significantly reduces the risk of dementia among men in certain racial and age groups, especially those who are aged 50 years and older and are African American.

  • One study published in the Annals of Family Medicine included data from 73,761 people who received care through the Veterans’ Health Administration from 2000 to 2015. While all participants did not use diabetes medication and dementia-free at baseline, they subsequently developed type 2 diabetes. The participants began treatment with either metformin or sulfonylurea. The researchers reported that, after controlling for confounding variables, among people aged 50 years and older, metformin versus sulfonylurea use was associated with a significantly lower risk of dementia. Porter said these results may point to one approach for reducing the risk of dementia in African Americans with type 2 diabetes. She noted that people with diabetes should continue to use metformin as a first-line therapy for those at risk of developing dementia or Alzheimer’s disease. The current information, she added, does not support the use of metformin by individuals without diabetes to prevent dementia.
  • A study of 17,000 veterans with diabetes found that taking metformin was associated with a lower risk of dementia than other diabetes drugs known as sulfonylureas (such as glyburide and glipizide.)

Side effects of metformin

Metformin helps control the amount of glucose in your blood. It decreases the amount of glucose to absorb from food and the amount made by your liver.

It is considered a safe medication. However, as with all drugs there are potential side effects and precautions.

The side effects can include:

  • Heartburn
  • Stomach pain
  • Nausea or vomiting
  • Bloating
  • Gas
  • Diarrhea
  • Weight loss
  • Headache
  • Unpleasant metallic taste in the mouth

Side effects may start when you start the medication and usually go away within a few weeks.

“The most serious but uncommon side effect metformin can cause is lactic acidosis,” said Porter. “Metformin has a ‘black box’ warning about this risk. A boxed warning is the most severe warning the Food and Drug Administration issues.”

“Metformin can decrease the levels of vitamin B-12 in your body,” Porter added. “This could result in anemia or low levels of red blood cells. If you have reduced vitamin B-12 or calcium dietary intake through your diet, you may be at higher risk of very low vitamin B-12 levels. Vitamin B-12 levels will improve if you stop taking metformin or take vitamin B-12 supplements. If you have mild or moderate kidney problems, your doctor may start you at a lower dosage of metformin. If you have acute heart failure or a recent heart attack, you should not take metformin. You should not take metformin if you have severe liver problems since your liver clears lactic acid from your body.”

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