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.

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.

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.

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 )