Cognitive function in the liraglutide cohort declined 18% slower than in the placebo arm over one year of treatment, researchers announced Tuesday at the Alzheimer’s Association International Conference.
Patients with mild Alzheimer’s disease who received an older Novo Nordisk GLP-1 drug experienced a slower rate of cognitive decline than their peers on placebo, researchers announced Tuesday.
The Phase IIb data reported at the Alzheimer’s Association International Conference come from a study that randomized 204 people at multiple sites in the UK to receive placebo or liraglutide, an older GLP-1 analogue that Novo Nordisk sells as Saxenda in obesity and Victoza in type 2 diabetes. Multiple observational studies and meta-analyses have linked type 2 diabetes to increased risk of Alzheimer’s.
Participants received daily subcutaneous injections for 12 months. The trial missed its primary endpoint, with the investigators finding liraglutide had no significant effect on cerebral glucose metabolic rate. However, the study did generate signs of efficacy on other measures of the patients’ health.
While the trial was not powered to assess cognitive changes, the researchers found brain function in the liraglutide cohort declined 18% slower than in the placebo arm over one year of treatment. The study assessed cognitive function on a composite score of 18 tests of memory, comprehension, language and spatial orientation. In patients who completed the trial, change in cognition was statistically significant.
The researchers also reported a statistically significant benefit on an exploratory brain volume endpoint. Measured by MRI, patients on liraglutide had nearly 50% less volume loss in several areas of the brain, including frontal, temporal, parietal and total gray matter. The parts of the brain with less volume loss are involved in tasks such as memory, language and decision-making that are affected by Alzheimer’s.
Paul Edison, the Imperial College London professor of science who led the study, said in a statement that “the slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart.” Edison, who noted the need for further research, said liraglutide may reduce brain inflammation, lower insulin resistance, limit the harm of amyloid-beta and tau, as well as improve nerve cell communication.
The proposed mechanisms of action are supported by preclinical work into the effect of GLP-1 medicines on brain health. Edison co-authored a review article in 2022 that described evidence the molecules cut tau phosphorylation and amyloid deposition while increasing synaptic function.
Preclinical evidence, coupled to observational data on the link between Alzheimer’s and diabetes, have encouraged researchers to study drugs such as liraglutide in the neurodegenerative disease. Novo is running three Phase III trials of oral and subcutaneous formulations of semaglutide, the active ingredient in Ozempic and Wegovy, in people with Alzheimer’s.
Semaglutide is more effective at supporting weight loss than the older liraglutide but it is unclear if the advantage extends to Alzheimer’s. The semaglutide studies have completion dates in 2025 and 2026, respectively.
The trials will put to the test what has interested researchers for more than a decade. The National Institute on Aging began testing the GLP-1 receptor agonist exenatide in Alzheimer’s in 2010 but terminated the study well short of the enrollment target after AstraZeneca withdrew its support. In 2012, the University of Aarhus started a trial to test liraglutide in Alzheimer’s but saw no changes in cognition.
