Data from a small clinical trial showed that a drug from the GLP-1 receptor agonist class, known for weight loss, slowed the loss of brain volume in people with mild Alzheimer's disease. The trial results, presented at the Alzheimer's Association International Conference, provided the first glimpse of how GLP-1 drugs may act on hard-to-treat brain disorders.
The trial studied 204 patients in Britain, half of whom received Novo Nordisk's earlier-generation GLP-1 drug liraglutide, and the other half a placebo. While the trial did not meet its primary endpoint, which was change in the cerebral glucose metabolic rate, an assessment of brain function, it did meet the secondary endpoints. The results showed that liraglutide appeared to reduce shrinking in the parts of the brain that control memory, learning, language, and decision-making by nearly 50% compared to placebo.
Although the trial was not sponsored by Novo Nordisk, the Danish drugmaker is currently testing its new-generation, more effective GLP-1 drug semaglutide—marketed as Ozempic for diabetes and Wegovy for obesity—in thousands of patients with early Alzheimer's. The two trials began in 2021, and results are expected in 2025.
Rebecca Edelmeyer, PhD, senior director of scientific engagement at the Alzheimer's Association, described the results published on Tuesday as "really intriguing," stating, "This is our first time really seeing this type of intervention readout in a clinical trial."
Researchers have previously suggested that diabetes regimens, from semaglutide to insulin and metformin, appear to address several different aspects of the metabolic system implicated in Alzheimer's, including a protein called amyloid and inflammation. The hope is that improving glucose utilization and reducing inflammation in the body, including the brain, could slow the progression of Alzheimer's.
However, it is important to note that the trial was not designed to measure cognitive benefits, and some scientists have urged caution in interpreting the results. Stephen Evans, emeritus professor at the London School of Hygiene and Tropical Medicine, stated that while the repurposing of drugs is an important avenue of research, there is a lot of uncertainty in this case. He cautioned that the observed shrinking in the memory and learning parts of the brain "may not translate to important cognitive benefits," and the results did not demonstrate that liraglutide could protect against dementia, though pursuing a larger trial would be worthwhile.
