Oral Semaglutide Falls Short in Alzheimer’s Study: Novo Nordisk

Novo Nordisk reports that its phase 3 Evoke and Evoke+ trials, which evaluated oral semaglutide in people with early-stage Alzheimer’s disease, did not meet their primary endpoints.

“We always knew that there would be a low likelihood of success but it was important to determine if semaglutide could take one of the medicine's most challenging frontiers based on the indicative data points we had," says Maziar Doustdar, President and CEO, Novo Nordisk.  

The Evoke program examined semaglutide, an oral GLP-1 treatment, as a possible therapy targeting metabolic pathways implicated in Alzheimer’s. Although the trials did not achieve their main goals, Novo Nordisk reports improvements in Alzheimer’s-related biomarkers. These findings have prompted discussion about the role of combination approaches as the field shifts beyond amyloid-targeting therapies.

Howard Fillit, Chief Science Officer, Alzheimer’s Drug Discovery Foundation (ADDF), says that the results reflect a broader shift in research strategy. He notes that current anti-amyloid drugs slow cognitive decline by about 30%, leaving significant unmet need. Approaches addressing other pathways may contribute to narrowing the remaining gap, particularly as the industry explores precision medicine strategies based on biomarker profiles.

The ADDF supported early work that helped enable Novo Nordisk’s trials, investing nearly US$1 million beginning in 2011 in a phase 2 study of liraglutide conducted at Imperial College London. That research advanced understanding of GLP-1 mechanisms in the brain and helped catalyze further funding from Novo Nordisk and GE HealthCare. The completion of Evoke and Evoke+ represents the most advanced testing to date of a GLP-1 candidate in Alzheimer’s disease.

GLP-1 receptor agonists have drawn significant global interest due to their established role in regulating insulin production, glucose levels, and appetite, which contributes to clinically meaningful weight loss. Although they are primarily approved for type 2 diabetes and obesity, emerging research continues to explore their potential effects beyond metabolic disease. Clinical trials have shown that GLP-1 medications can reduce the risk of major cardiovascular events, such as heart attack and stroke, further broadening scientific interest in their mechanisms.

“For now, semaglutide’s story remains firmly rooted in its proven ability to transform diabetes and obesity care as well as cardiovascular risk reductions and other comorbidities where its impacts continue to grow globally,” says Doustdar.

While the latest Novo Nordisk’s results fell short of primary endpoints, experts maintain that studying metabolic pathways remains essential to broadening the therapeutic landscape. More than 70% of the current Alzheimer’s pipeline is focused on novel targets, underscoring the sector’s interest in combination strategies and earlier interventions.

Alzheimer’s Disease in Mexico

According to the 2021 World Alzheimer Report, an estimated 55 million people worldwide are living with dementia, with Alzheimer’s disease representing the majority of cases. That figure is projected to rise to 78 million by 2030. In Mexico, an estimated 7.8% of adults over the age of 60 are living with Alzheimer’s disease, reports Mexico’s Ministry of Health.

While Alzheimer's is more prevalent among individuals over the age of 65, early-onset cases can manifest as early as 40 to 50 years of age, as reported by IMSS. Nevertheless, most cases are diagnosed in older adults, making it the leading cause of dementia in this demographic. The aging of Mexico’s population will lead to an increase in cases of Alzheimer's disease, says Carlo Andrés Briones, Medical Director, Quest Diagnostics.