Top-line Results from evoke and evoke+: Two Phase 3, Randomized, Placebo-controlled Trials of Semaglutide in Participants with Early-stage Symptomatic Alzheimer’s Disease
Jeffrey L. Cummings1, Alireza Atri2, Howard H. Feldman3, Mary Sano4, Henrik Zetterberg5, Paul Mystkowski6, Filip K. Knop7, Peter Johannsen7, Teresa León7, Rikke Mortensen Abschneider7, Philip Scheltens8
1Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada Las Vegas, 2Banner Sun Health Research Institute, 3Alzheimer’s Disease Cooperative Study, Department of Neurosciences, University of California San Diego, 4Icahn School of Medicine at Mount Sinai, 5Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 6Novo Nordisk Inc., 7Novo Nordisk A/S, 8Alzheimer Center, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC
Objective:
To assess the efficacy and safety of semaglutide to slow Alzheimer’s disease (AD) progression.
Background:

Semaglutide, a glucagon-like peptide-1 receptor agonist, is a promising candidate to slow AD progression through a multifaceted mechanism of action, including modulating neuroinflammation and potentially reducing neurodegeneration. The evoke (NCT04777396) and evoke+ (NCT04777409) phase 3 trials investigate the efficacy and safety of semaglutide versus placebo in participants with early-stage symptomatic AD. Here, we report top-line results for the primary and key secondary endpoints for evoke and evoke+ at 2 years.

Design/Methods:

evoke and evoke+ are randomized (1:1), double-blind, parallel-group trials investigating the efficacy and safety of semaglutide versus placebo in participants with early-stage symptomatic AD. Participants received semaglutide 14mg orally or placebo for 3 years with a 5-week follow-up period. Flexible dosing allowed for extension of dose-escalation intervals, dose reduction and treatment pauses. Inclusion criteria were adults aged 55–85 years with mild cognitive impairment, defined by a Clinical Dementia Rating (CDR) global score of 0.5, with a CDR domain score of ≥0.5 in ≥1 of three activities (personal care, home and hobbies, and community affairs), or mild dementia of Alzheimer’s type (CDR global score of 1.0). evoke+ also included participants with significant small vessel co-pathology. All participants had confirmed amyloid pathology with positron emission tomography or cerebrospinal fluid analysis. The primary objective is to compare semaglutide–placebo change in the CDR–Sum-of-Boxes score from baseline to week 104.

Results:

We will be reporting the 2-year top-line results, including safety and tolerability. The trials will continue for 1 additional year without breaking the blind.

Conclusions:

Results from evoke and evoke+ will be presented at a scientific conference in 2026. Novo Nordisk thanks evoke and evoke+ participants, their families, investigators, site personnel and everyone involved in the trials.

Previously presented at CTAD25 and published in JPAD (Cummings et al. 2025;DOI:TBC )

10.1212/WNL.0000000000216975
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.