GLP-1 trial in Alzheimer’s comes up empty (and why that is not the whole story)

On November 24, 2025, Novo Nordisk reported topline results from EVOKE and EVOKE+, two phase 3 trials of oral semaglutide in people who already had early symptomatic Alzheimer’s. Across roughly 3,800 participants over 2 years, the drug did not slow disease progression on the primary cognitive endpoint (the CDR-SB), and the secondary measures did not rescue it. It did move some Alzheimer’s biomarkers, but that did not translate into a clinical benefit.

The teaching point matters more than the result. Treating established disease is a different question from preventing it years earlier. So a negative treatment trial does not settle the prevention question, and it should not be read as one.

It also does not validate the hopeful headlines. The large observational signal that “GLP-1 drugs lower dementia risk” comes from people who choose or qualify for these drugs, a setup that is prone to bias and routinely overstates effects. A clean negative trial here is a useful reminder to weight a randomized result over an observational one.

The honest caveat: dedicated prevention trials are still running, and the oral semaglutide tested here is not identical to the injectable versions or to tirzepatide, so this is one drug in one setting, not the whole class.

Full context in our deep dive on GLP-1 drugs and the brain. Primary source: Novo Nordisk’s topline announcement, 2025. This is education, not medical advice.