Could Ozempic slow Alzheimer’s progression?
MDlinx Aug 02, 2024
Liraglutide—a once-daily, injectable GLP-1 drug for obesity and diabetes—may protect the brains of people with mild Alzheimer’s disease (AD), according to a mid-stage study presented in July 2024 at the Alzheimer’s Association International Conference (AAIC) in Philadelphia.
From The Alzheimer’s Association International Conference 2024: GLP 1 Drug Liraglutide May Protect Against Dementia [press release]. Alzheimer’s Association. July 30, 2024.
After 1 year of treatment, patients who took liraglutide had as much as an 18% slower decline in their cognitive function vs those who took placebo.
Kim A. Older GLP-1 drug from Novo Nordisk may slow Alzheimer’s disease progression by protecting the brain, study says. CNBC. July 30, 2024.
The drug achieved this by slowing brain shrinking—which often occurs in AD as nerves break down and malfunction—in areas needed for memory, learning, language and decision-making.
“This research provides hope that more options for changing the course of the disease are on the horizon,” Alzheimer’s Association chief science officer and medical affairs lead Maria C. Carrillo, PhD, said in a press release.
From The Alzheimer’s Association International Conference 2024: GLP 1 Drug Liraglutide May Protect Against Dementia [press release]. Alzheimer’s Association. July 30, 2024.
Repurposing liraglutide
Liraglutide is approved in the US under the brand names Saxenda (for weight loss) and Victoza (for diabetes).
“Repurposing drugs already approved for other conditions has the advantage of providing data and experience from previous research and practical use,” Dr. Carrillo noted. “So we already know a lot about real-world effectiveness in other diseases and side effects.”
From The Alzheimer’s Association International Conference 2024: GLP 1 Drug Liraglutide May Protect Against Dementia [press release]. Alzheimer’s Association. July 30, 2024.
In preclinical studies, GLP-1 drugs such as liraglutide have been shown to protect the nervous system, normalize the glucose processing by the brain, lower early forms of amyloid, and improve learning and memory.
From The Alzheimer’s Association International Conference 2024: GLP 1 Drug Liraglutide May Protect Against Dementia [press release]. Alzheimer’s Association. July 30, 2024.
About the mid-stage study
Researchers at Imperial College London in the UK recruited 204 patients with mild AD. The patients underwent memory testing, MRI to evaluate the structure and volume of their brains, and PET brain imaging to test glucose metabolism. The patients were randomly assigned a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 1 year. The memory tests and brain scans were repeated at the end of the study.
From The Alzheimer’s Association International Conference 2024: GLP 1 Drug Liraglutide May Protect Against Dementia [press release]. Alzheimer’s Association. July 30, 2024.
The primary endpoint—the change in the cerebral glucose metabolic rate in the cortical regions of the brain—was not met. Study lead Paul Edison, MD, PhD, suggested that the trial did not have enough participants to show a significant change in this rate.
Kim A. Older GLP-1 drug from Novo Nordisk may slow Alzheimer’s disease progression by protecting the brain, study says. CNBC. July 30, 2024.
However, the study met its secondary endpoint of change in clinical and cognitive measure scores and an exploratory goal of brain volume.
The cognitive function score was based on 18 tests for memory, comprehension, language and spatial orientation (ADAS EXEC z score).
The 79 patients who completed 1 year of liraglutide treatment experienced a significant slowing of cognitive decline vs 87 patients who completed 1 year of placebo. MRI showed that patients who received liraglutide had nearly 50% less volume loss in the frontal, temporal and parietal areas of the brain and total grey matter—areas responsible for several functions often altered by AD, including memory and language.
From The Alzheimer’s Association International Conference 2024: GLP 1 Drug Liraglutide May Protect Against Dementia [press release]. Alzheimer’s Association. July 30, 2024.
Further research
“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” said Dr. Edison. “While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid-beta and tau, and improving how the brain’s nerve cells communicate.”
From The Alzheimer’s Association International Conference 2024: GLP 1 Drug Liraglutide May Protect Against Dementia [press release]. Alzheimer’s Association. July 30, 2024.
The most common adverse events were gastrointestinal, such as nausea, representing 25.5% of all adverse events in patients who received liraglutide.
“Having a drug which has got a very good safety profile and could be used widely—it will change the field significantly,” Dr. Edison said.
Kim A. Older GLP-1 drug from Novo Nordisk may slow Alzheimer’s disease progression by protecting the brain, study says. CNBC. July 30, 2024.
If approved for AD, GLP-1 drugs, “could be administered pretty much anywhere in the world without a huge amount of monitoring” for side effects, suggesting “a great potential” for these drugs.
However, further research is needed. Dr. Edison is involved in two late-stage trials assessing GLP-1 drug semaglutide, the active ingredient in Ozempic and Wegovy, in nearly 2,000 patients with AD.
What this means for you
Liraglutide may protect the brains of people with mild AD by slowing shrinking in key areas of the brain. Patients prescribed the GLP-1 agonist showed a slower decline in their cognitive function vs those on placebo. While more research is needed to confirm the findings, early study results prove promising.
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