Drugs like Ozempic and Wegovy could significantly cut dementia risk

Diabetes and weight loss treatments such as Ozempic and Wegovy, known as GLP-1 agonists, could significantly reduce the risk of developing any type of dementia, according to a meta-analysis of 26 clinical trials with more than 160,000 participants.

The treatments, which include medications like semaglutide, liraglutide and exenatide, have been linked to a slightly reduced dementia risk before, but this was based on observational studies looking at health records.

Now, Catriona Reddin at the University of Galway in Ireland and her colleagues have combined the results of randomised trials where a range of GLP-1 drugs were given to people with type 2 diabetes who hadn’t yet been diagnosed with dementia or cognitive impairment, tested against a placebo. They found that taking these drugs seemed to significantly reduce the risk of developing dementia or cognitive impairment during the trials’ minimum six-month follow-up periods.

“The gold standard would be one large, randomised trial to answer this question, but this definitely adds another stream of evidence [to past studies],” says Ziyad Al-Aly at Washington University School of Medicine in St. Louis, Missouri, who wasn’t involved in this research.

Diabetes may be a risk factor for dementia, so it has been suggested that just controlling blood sugar levels produces this protective effect. For instance, a study by Jingchuan Guo at the University of Florida and her colleagues suggests that a class of diabetes drugs called SGLT2 inhibitors, which lower blood sugar levels by helping the kidneys remove excess glucose, may reduce the risk of Alzheimer’s disease or related kinds of dementia, based on people’s health records.

But in Reddin and her team’s placebo-controlled analysis, SGLT2 inhibitors weren’t linked to a reduced dementia risk, which suggests that the protective effects of GLP-1 drugs go beyond just blood sugar control.

Although the exact mechanism is unclear, these drugs have been linked to reduced inflammation, with neuroinflammation increasingly being recognised as a cause of dementia. By reducing chronic inflammation, they may slow cell death in the brain, says Reddin.

GLP-1 drugs may also protect against cardiovascular problems, such as plaque build-up in the arteries and high blood pressure, which could otherwise cause dementia.

“All roads seem to be leading to Rome. We can see from multiple observational studies and now an analysis of placebo-controlled studies that these medications have this [anti-dementia] effect,” says Al-Aly.

Al-Aly stresses that we aren’t yet at a place where someone who is at an increased risk of developing dementia would be prescribed GLP-1 drugs to lower their odds. But he also says doctors may consider offering these medications over other glucose-lowering ones to people with type 2 diabetes who are also at an increased risk of cognitive decline, for example if they had a family history of the condition. “This research will increase a physician’s propensity for prescribing these medications,” he says.

Reddin notes that the analysis’ minimum six-month follow-up period was relatively short, and says “large trials should be conducted to specifically study the effect of glucose-lowering therapy on dementia and cognitive decline”. Two clinical trials investigating semaglutide as a therapy for early Alzheimer’s disease are expected to conclude this year.