Exploring GLP-1 drugs as preventive therapy may still hold promise within broader strategy targeting Alzheimer's pathways beyond amyloid, ADDF notes

SAN DIEGO, Dec. 4, 2025 /PRNewswire/ -- Today, Novo Nordisk presented new topline results from their Evoke and Evoke+ phase 3 trials of semaglutide, an oral GLP-1 drug, at the Clinical Trials on Alzheimer's Disease (CTAD) conference. While the trials did not meet their primary endpoints, the presentation highlighted biomarker findings that offer further insight into Alzheimer's pathobiology and underscored a critical shift toward the next era of drug development, which will target the many interrelated biological drivers of this complex disease.

"While the data presented at CTAD was disappointing, pursuing this type of high-risk, high-reward research into Alzheimer's pathobiology is essential to deepening our understanding of the disease and continuing to advance the science," said Howard Fillit, MD, Co-Founder and Chief Science Officer of the Alzheimer's Drug Discovery Foundation (ADDF). "Even negative trials move the field forward as they still teach us something. If we look to the early anti-amyloid studies, which were also negative, they offered critical lessons that informed later trials and ultimately helped bring drugs like Leqembi and Kisunla to market. As we dig further into the data, there is much we can learn, including exploring the potential of GLP-1 drugs as a preventive therapy, which may still hold promise."

The Evoke trials were robust and rigorous, providing crucial learnings that will help refine future study designs and guide the evaluation of other drugs targeting metabolic and inflammatory pathways. The results presented by Novo Nordisk demonstrated reductions of up to 10% in biomarkers linked to neuroinflammation and Alzheimer's disease – a statistically significant change, but not large enough to have a clinical impact.

The ADDF has long championed a research strategy that targets the full pathobiology of Alzheimer's, and invested early in science that laid the groundwork for the Evoke trials, providing nearly $1 million beginning in 2011 to support Dr. Paul Edison's pioneering phase 2 study of liraglutide, an early generation injectable GLP-1 medication.

"The metabolic pathway remains a compelling area of investigation, and we will continue to pursue rigorous studies to determine how therapies targeting these mechanisms can be optimized and combined to achieve greater impact for patients," said Paul Edison, MBBS, PhD, FRCPI, Professor of Neuroscience in the Faculty of Medicine at Imperial College London.

"With more than 70% of the Alzheimer's drug pipeline now focused on non-amyloid targets, the field is moving steadily toward an era of precision medicine and combination therapies," added Dr. Fillit. "The Evoke trials are an important part of this progress, demonstrating how large-scale studies of novel pathways can deepen our understanding of Alzheimer's biology. Even when primary endpoints are not met, biomarker and mechanistic data help illuminate how best to refine, repurpose, or combine therapies. This is exactly how combination treatment strategies have evolved in cancer – and it is the direction Alzheimer's research must continue to move."

Full results from the Evoke and Evoke+ trials will be presented at the International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) in Copenhagen in March 2026.

About The Alzheimer's Drug Discovery Foundation (ADDF)
Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer's Drug Discovery Foundation is dedicated to rapidly accelerating the development of drugs to prevent, treat, and cure Alzheimer's disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer's, employing a venture philanthropy model to support research in academia and the biotech industry. The ADDF's leadership and contributions to the field have played a pivotal role in bringing the first Alzheimer's PET scan (Amyvid®) and blood test (PrecivityAD®) to market, as well as fueling the current robust and diverse drug pipeline. Through the generosity of its donors, the ADDF has awarded more than $370 million to fund 765 Alzheimer's drug development, biomarker, and prevention programs in 21 countries. To learn more, please visit:  http://www.alzdiscovery.org/.

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SOURCE Alzheimer's Drug Discovery Foundation