Key Takeaways
- A GLP-1 agonist — the class of drugs shown to help with
diabetes and weight loss and reduce the risk of heart disease —
also may protect the brain.
- In a Phase 2b trial,
liraglutide appears to reduce shrinking in the parts of the brain
that control memory, learning, language and decision-making by
nearly 50% compared to placebo.
PHILADELPHIA, July 30,
2024 /CNW/ -- A glucagon-like peptide-1 (GLP-1)
drug appears to slow cognitive decline by protecting the brain,
according to Phase 2b clinical trial
data reported today at the Alzheimer's Association International
Conference® (AAIC®) 2024, in Philadelphia and online.
GLP-1 receptor agonists, which mimic the natural hormone
glucagon-like peptide released by the stomach after eating, can
help people manage diabetes, lose weight and lower their risk of
heart disease, stroke and kidney disease. Research in animal models
of Alzheimer's disease suggests these drugs may have
neuroprotective effects, reduce early forms of amyloid, normalize
the brain's processing of glucose, and improve memory and learning.
Liraglutide (Novo Nordisk) likely works by multiple mechanisms in
the brain.
This new research reported at AAIC 2024 suggests liraglutide may
protect the brains of people with mild Alzheimer's disease and
reduce cognitive decline by as much as 18% after one year of
treatment compared to placebo by slowing the shrinking of the parts
of the brain that are vital for memory, learning, language and
decision-making.
"We are in an era of unprecedented promise, with new treatments
in various stages of development that slow or may possibly prevent
cognitive decline due to Alzheimer's disease," said Maria C. Carrillo, Ph.D., Alzheimer's
Association chief science officer and medical affairs lead. "This
research provides hope that more options for changing the course of
the disease are on the horizon.
"Repurposing drugs already approved for other conditions has the
advantage of providing data and experience from previous research
and practical use — so we already know a lot about real-world
effectiveness in other diseases and side effects," Carrillo
added.
The Alzheimer's Association Part the Cloud research grants
program has invested more than $82
million to advance 68 clinical trials targeting a variety of
compounds, including repurposed drugs, addressing known and
potential new aspects of the disease.
The randomized, double-blind, placebo-controlled Evaluating the
Effects of the Novel GLP-1 Analogue Liraglutide in Alzheimer's
Disease (ELAD) trial led by Prof. Paul
Edison, M.D., Ph.D., professor of science from Imperial
College London, included 204 patients with mild Alzheimer's disease
seen at 24 clinics throughout the United
Kingdom. Each received a daily subcutaneous injection for
one year: half (102) received up to 1.8 mg of liraglutide and half
(102) received a placebo. Before the study began, all patients had
magnetic resonance imaging (MRI) to evaluate brain structure and
volumes, glucose metabolism PET scans and detailed memory testing.
These were repeated at the end of the study with regular safety
visits.
The study's primary endpoint was change in the cerebral glucose
metabolic rate in the cortical regions of the brain (hippocampus,
medial temporal lobe and posterior cingulate), which was not met.
However, the secondary endpoint of change in scores for clinical
and cognitive measures and the exploratory endpoint of brain volume
showed statistically significant benefit.
"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."
Edison added that those in the study who received liraglutide
had nearly 50% less volume loss in several areas of the brain,
including frontal, temporal, parietal and total gray matter, as
measured by MRI. These areas are responsible for a variety of
critical functions that often are affected by Alzheimer's disease,
including memory, language and decision-making.
Researchers also conducted cognitive testing in the patients —
before treatment and at 24 and 52 weeks. Although the study was not
powered to assess cognitive changes, researchers found that
patients who received liraglutide had an 18% slower decline in
cognitive function in a year compared to those who got the
placebo.
Cognitive function was calculated as a composite score of 18
different tests of memory, comprehension, language and spatial
orientation (ADAS EXEC z score). For those in the study who
completed 52 weeks of treatment (treatment n=79, placebo n=87),
those taking the drug saw a statistically significant slowing of
cognitive decline (p<0.01).
Gastrointestinal problems such as nausea were the most common
side effects, which totaled 25.5% of all adverse events in the
liraglutide group. Twenty-five serious side effects occurred in 18
participants (17.6%) in the placebo arm and seven participants
(6.9%) in the treatment arm. Most serious side effects were
considered unlikely to be related to the study treatment, Dr.
Edison said.
Well-positioned to test this further are current late-stage
clinical trials of GLP-1 analogues, several of which are ongoing.
For example, EVOKE Plus is a 3-year clinical trial of semaglutide
in more than 1,800 people with early Alzheimer's disease. Note: Two
brands of liraglutide have been approved by the U.S. Food and Drug
Administration, one for weight loss (Saxenda) and the other for
diabetes (Victoza).
About the Alzheimer's Association International
Conference® (AAIC®)
The Alzheimer's
Association International Conference (AAIC) is the world's largest
gathering of researchers from around the world focused on
Alzheimer's and other dementias. As a part of the Alzheimer's
Association's research program, AAIC serves as a catalyst for
generating new knowledge about dementia and fostering a vital,
collegial research community.
AAIC 2024 home page: www.alz.org/aaic/
AAIC 2024 newsroom: www.alz.org/aaic/pressroom.asp
AAIC 2024 hashtag: #AAIC24
About the Alzheimer's Association®
The
Alzheimer's Association is a worldwide voluntary health
organization dedicated to Alzheimer's care, support and research.
Our mission is to lead the way to end Alzheimer's and all other
dementia — by accelerating global research, driving risk reduction
and early detection, and maximizing quality care and support. Our
vision is a world without Alzheimer's and all other
dementia®. Visit alz.org or call 800.272.3900.
- Paul Edison, M.D., Ph.D., et al.
Evaluation of Novel GLP-1 analogue in the treatment of Alzheimer's
disease. (Funding: Alzheimer's Society, UK; Alzheimer's Drug
Discovery Foundation, Novo Nordisk AS, John and Lucille Van Geest
Foundation, National Institute for Health and Care Research (NIHR)
Biomedical Research Centre).
*** AAIC 2024 news releases may contain updated data that does
not match what is reported in the following abstract.
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SOURCE Alzheimer's Association