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A Diabetes Drug for Dementia?

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Pharmacists call them “multitarget drugs.” They’re medications that were developed for one purpose and then found to be effective in treating something else. Aspirin is a familiar example. Originally used to treat pain, many physicians advise it as a way to prevent heart attack and stroke. Similarly, birth control pills have been found to be useful in treating acne.

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According to new reports, the drug dulaglutide (brand name Trulicity) also appears to be a multitarget medication. This column recently reported that dulaglutide, which is an injectable prescription medicine for adults with type 2 diabetes, had been approved by the U.S. Food and Drug Administration (FDA) as a way of lowering the risk of major cardiovascular events (MACE) in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. Now a new study has reported another possible use for dulaglutide — to lower cognitive decline and prevent dementia in people with type 2. This was an important finding because type 2 diabetes is a known risk factor for cognitive impairment and dementia

The new study, which was published in the medical journal Lancet Neurology, was based on what’s known as the REWIND (Researching Cardiovascular Events with a Weekly Incretin in Diabetes) study, which was a randomized, double-blind study carried out at 371 sites in 24 countries. REWIND formed the basis for the FDA’s approval of dulaglutide for MACE and now the new report indicates dulaglutide could also reduce cognitive impairment in adults ages 50 and above who have established or newly diagnosed type 2 diabetes along with additional cardiovascular risk factors.

The researchers looked at data from 8,828 patients who were part of the REWIND trial. The patients had an average age of 65.5 and the male-female split was about 50-50. They had an HbA1c (measure of glucose control over the previous 2 to 3 months) of 9.5% or less and were taking no more than two blood-sugar-lowering agents. The patients also had histories of heart attack, stroke, chest pain and the like. They were randomly divided into groups: one was given weekly doses of dulaglutide and the other was given a placebo (an inactive substance). The patients were given cardiovascular follow-ups every six months. The trial lasted two years (2011 to 2013) and the subjects were followed up for approximately five years. Cognitive decline was measured by means of two tests — the Montreal Cognitive Assessment or the Digit Symbol Substitution Test.

After adjusting for individual standardized baseline scores, the researchers determined that the risk of “substantive cognitive impairment” was reduced by 14% in those given dulaglutide. The researchers considered the possibility that those patients who showed cognitive decline might have suffered strokes, but, according to study author Hertzel Gerstein, MD, of McMaster University in Hamilton, Ontario, their findings did “not support the hypothesis that stroke was the reason for the effect on cognitive impairment — but it does not rule it out — and suggests that other mechanisms may be at play.” He then went on to say, “…a benefit on both cognitive impairment and stroke suggests that perhaps the therapy has some neuroprotective effects.”

Dulaglutide is what’s known as a glucagon-like peptide-1 (GLP-1) receptor agonist, a class of drugs that helps diabetes patients achieve blood sugar control. Others include exenatide (Byetta, Bydureon), liraglutide (Victoza), semaglutide (Ozempic) and lixisenatide (Lyxuimia). This raises the possibility that these drugs might also have a beneficial effect on dementia and cognitive decline. The study published in Lancet Neurology was accompanied by an editorial by Geert Jan Biessels, MD, of the UMC Brain Center at the University Medical Center Utrecht in the Netherlands. Biessels, whose special area of research is vascular causes of cognitive impairment and dementia, wrote, “If some classes of anti-diabetic drugs are superior than others in preventing dementia, this finding has clinical implications…. The effect of this drug class on dementia and related diseases in people with diabetes and those without diabetes urgently needs to be studied.”

Want to learn more about maintaining cognitive health with diabetes? Read “Nine Tips to Keep Your Memory With Diabetes,” “Keeping Your Brain Strong With Diabetes” and “Memory Fitness: How to Get It, How to Keep It.”



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