Failures in studies raise doubts about Novo Nordisk's GLP-1 as Alzheimer's treatment

SAN DIEGO, Dec 3 Recent results from two major clinical studies indicate that Novo Nordisk's GLP-1 medication, semaglutide, shows no cognitive benefit for individuals in the early stages of Alzheimer's disease. The findings were presented at a medical conference on Wednesday, ending optimism that the widely used drug could slow cognitive decline in such patients.

The Danish pharmaceutical company announced last week that the studies, which aimed to demonstrate that the semaglutide pill Rybelsus could reduce Alzheimer's progression by at least 20%, failed to achieve this objective. Although minor improvements were observed in some biological markers, they were insufficient to impact cognitive deterioration.

Both trials, involving 3,800 participants with confirmed Alzheimer's, revealed that Rybelsus did not alter the rate of decline in clinical dementia scores over two years compared to a placebo. I don't see that it affects anything likely to impact Alzheimer's disease, stated Dr. Mary Sano, a Mount Sinai Alzheimers researcher involved in the studies.

Alzheimers disease progressively impairs memory and thinking abilities, with characteristic brain changes such as amyloid beta plaques and tau tangles leading to neuronal loss. The trials showed reductions of up to 10% in certain Alzheimers biomarkers, particularly measures of tau, but most effects remained under 10%. Amyloid removal needs to be much more rigorous to observe a noticeable effect, Dr. Sano added.

Currently, only two drugsEli Lillys Kisunla and Eisai-Biogens Leqembihave been approved to slow Alzheimers progression by targeting amyloid deposits, demonstrating roughly a 30% delay in disease advancement in trials.

Novo reported that Rybelsus maintained a safety profile consistent with its approved use for diabetes. Semaglutide, also marketed as weekly injections Ozempic (for diabetes) and Wegovy (for weight loss), is known to cause side effects such as nausea.

Much of the prior evidence suggesting cognitive benefits from GLP-1 medications came from population studies of diabetes patients. Novo highlighted potential biases in these studies, noting that patients receiving GLP-1 treatment may have better access to endocrinologists and belong to higher socioeconomic groups, which could overstate the drugs effects.

Peter Johannsen, Novos international medical vice president, emphasized these factors on Tuesday. A company spokesperson stated that both trials will be discontinued and all data reviewed, adding that it is too early to predict further Alzheimers research plans. Complete results from the Rybelsus studies are expected at the 2026 Alzheimers and Parkinsons Disease Conferences in March.

Author’s Analysis: Semaglutide Shows No Cognitive Benefit in Early Alzheimer’s

Recent trial results confirm that Novo Nordisk’s semaglutide, marketed as Rybelsus, does not slow cognitive decline in patients with early-stage Alzheimer’s disease. Both studies, including 3,800 participants, failed to meet the primary endpoint of a 20% reduction in disease progression. Minor improvements in tau biomarkers were observed, but effects remained under 10% and insufficient to affect clinical outcomes.

These findings challenge previous observational studies suggesting cognitive benefits from GLP-1 medications in diabetes patients, highlighting potential confounding factors such as socioeconomic status and healthcare access. Dr. Mary Sano, a lead researcher, emphasized that the reductions in amyloid and tau were not robust enough to change disease trajectory.

While semaglutide continues to demonstrate a safe profile consistent with its diabetes and weight-loss indications, its role in Alzheimer’s appears limited. Only therapies specifically targeting amyloid, such as Eli Lilly’s Kisunla and Eisai-Biogen’s Leqembi, have shown measurable slowing of disease progression. Novo Nordisk plans to review all trial data, with full results expected at the March 2026 Alzheimer’s and Parkinson’s Disease Conferences.

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• Details of failed studies cast pall on Novo Nordisk's GLP-1 as Alzheimer's treatment

Author: Maya Henderson
Maya Henderson is a journalist focused on technology and startups. She has experience in leading IT publications and excels at conducting interviews and creating visual content.