Scientists have failed to show that weight-loss wonder drug semaglutide slows the progress of Alzheimer's disease (AD), as two-year clinical trials end in disappointment for patients, medical scientists and drugmaker Novo Nordisk.
In February 2024, we covered the news that researchers at the University of Toronto had found an intriguing – and potentially groundbreaking – way that GLP-1 agonists were able to reduce inflammatory markers, positioning medication like Wegovy and Ozempic as possible neurological lifelines. Because of this and other promising signs in preclinical research, there were naturally a lot of eyes on these trials.
However, Novo Nordisk has now announced that the top-line results from its two-year Phase 3 trials investigating semaglutide and early-stage symptomatic AD has failed to deliver on its core measure – despite some positive aspects when it came to symptom relief.
In two randomized, double-blinded trials featuring 3,808 adults, an older version of the company's oral semaglutide was tested for its efficacy and safety in reducing the progression of AD, compared with a placebo. Pre-clinical research had scientists cautiously optimistic about yet another treatment path for semaglutide – and in an area of medicine that desperately needs a major drug breakthrough.
While Novo Nordisk was well aware that repurposing semaglutide to halt AD progression was a long shot, there was a lot of hope – as well as time and money – invested in these trials. Some of the disappointment may also stem from how we view GLP-1 drugs: if they can change the course of obesity across the US, and the world, maybe they could succeed with AD when nothing else has? After all, semaglutide has been granted permission to treat chronic conditions like kidney disease and cardiovascular disease, and further studies are looking at its usefulness to combat addiction and much more. So we may not yet be ready to accept that the "miracle drug" does have limitations.
“Based on the significant unmet need in Alzheimer’s disease as well as a number of indicative data points, we felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success," Martin Holst Lange, chief scientific officer and executive vice president of Research and Development at Novo Nordisk. “While semaglutide did not demonstrate efficacy in slowing the progression of Alzheimer’s disease, the extensive body of evidence supporting semaglutide continues to provide benefits for individuals with type 2 diabetes, obesity and related comorbidities.”
Semaglutide actually resulted in improvements in Alzheimer’s disease-related biomarkers across the two Phase 2 trials, but sadly this didn't also mean it slowed down disease progression – which was the focus of the studies. Semaglutide did no better than a placebo in moving the needle on the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score, with no meaningful shift from baseline measures.
Novo Nordisk announced that a one-year extension of the two trials would now be discontinued. Their respective top-line results will be presented at the Clinical Trials in Alzheimer’s Disease (CTAD) conference on December 3, and full results will be available at the 2026 Alzheimer’s and Parkinson’s Diseases Conferences in March 2026.
Not surprisingly, the pharmaceutical giant's shares also took a big hit after the announcement.
Source: Novo Nordisk
