From social media to ads featuring an earworm jingle, it’s hard to escape hearing about Ozempic. Hailed for its game-changing effect on diabetes and obesity, semaglutide, the generic medication sold under the brand name Ozempic, is now being studied for its effectiveness on another deadly disease — Alzheimer’s.
The Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at The University of Texas Health Science Center at San Antonio is participating in two worldwide studies, EVOKE and EVOKE+, to determine the efficacy and safety of using semaglutide medications to delay early-onset dementia.
Rose Ann Barajas, Biggs Institute project coordinator, said San Antonio is in the uncommon position of having a twin epidemic of both diabetes and dementia among the city’s Hispanic population.
“I believe that’s why we were chosen to participate in the study,” she said. “We have the opportunity to impact a community that is in need of a treatment like this.”
The relationship between age, diabetes and dementia
According to the Alzheimer’s Association, 1 in 9 people 65 years and older in the United States have Alzheimer’s. After age 65 and as individuals age, the percentage increases. The U.S. Census Bureau reports that the fastest-growing segment of the nation’s population is 65 and older. In Bexar County, people 65 and older make up 12.5% of the population, while more than half of residents are Hispanic.
In San Antonio, 1 in 6 adults has Type 2 diabetes and 1 in 3 are pre-diabetic, Barajas said. She said Hispanics are 1.5 times more likely to develop dementia.
“It has been known for many years that Type 2 diabetes increases the risk for strokes and heart disease. Some studies suggest that diabetes also increases the risk for dementia,” she said. “The entire research team takes heed of all the reasons why the eventual findings from the EVOKE studies may have a positive impact here.”
Semaglutide medications mimic the naturally produced hormone glucagon-like peptide-1 or GLP 1. The medication, glucagon-like peptide-1 receptor agonist or GLP-1 RA, stimulates the pancreas to release more insulin when blood sugar is high, prevents the liver from making and releasing too much sugar and slows the stomach emptying. And, as seen in one testimonial after another, dramatic weight loss is an added benefit.
How can a medication used to manage Type 2 diabetes and obesity be effective against the early stages of dementia?
“If you have diabetes at the age of 55, your risk of developing dementia sometime before you die is nearly 350% higher than if you don’t
have diabetes,” said Sudha Seshadri, MD, a neurologist and founding director of the Biggs Institute.
According to the Alzheimer’s Association, diabetes raises the risk for heart disease, which damages the heart and blood vessels, including vessels in the brain. Damaged brain blood vessels could contribute to the development of Alzheimer’s.
Seshadri said the brain is the organ that gets the most blood per gram. Having heart disease and diabetes, which often go hand in hand, can lead to vascular brain injury.
“Vascular brain injury, even if it doesn’t cause Alzheimer’s, reduces the brain’s resistance to developing Alzheimer’s and other pathology,” she said.
But it’s not just damaged blood vessels that could lead to Alzheimer’s. Glucose is fuel for the brain and every cell in the body. Too much blood sugar, associated with Type 2 diabetes, can damage the brain and other organs and can cause inflammation, which can damage brain cells.
Participants sought for final stage of studies
During phase 1 and phase 2 of the study, there was an indication that doses of semaglutide may have positively affected Alzheimer’s disease. Barajas said researchers saw an improvement in memory function and a reduction in abnormal brain proteins and plaque. They also saw reduced inflammation in the brain and throughout the body.
The final stage of the study is three years and four months and expands the number of human participants to 1,840. Study participants must be age 55 to 85 and have early Alzheimer’s disease. The study is a double-blind placebo study, meaning some participants will take a semaglutide pill for close to three years while others will take an inactive placebo.
“However, a monitoring team periodically checks all the results and if there is a very clear benefit of the drug over placebo in interim analyses, they can advise to stop the study early and offer all study participants the active drug,” Seshadri said.
Participants will undergo a series of tests to determine if they have mild dementia and meet other eligibility requirements. Barajas said in most Alzheimer’s studies, people with small strokes or other signs of vascular brain injury cannot participate. That’s not the case for this pair of studies, EVOKE and EVOKE+.
Researchers at the Biggs Institute are recruiting participants for the EVOKE study. To sign up, contact Rose Ann Barajas at Barajasr@uthscsa.edu or call 210-450-8219.