At the 18th Clinical Trials on Alzheimer’s Disease (CTAD) conference in December 2025, topline results were presented from the evoke and evoke+ phase 3 clinical trials evaluating oral semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in participants with early-stage symptomatic Alzheimer’s disease (AD). Semaglutide is currently used to manage type 2 diabetes, by improving blood sugar control and decreasing appetite. The evoke randomised, double-blind, placebo-controlled studies represent some of the largest trials to date investigating a GLP-1 RA in AD, enrolling a combined total of 3,808 adults aged 55–85 years with mild cognitive impairment (MCI) or mild dementia due to AD confirmed by amyloid biomarkers. In both evoke and evoke+, participants received once-daily oral semaglutide or with a planned 2-year primary treatment phase and a subsequent 12-month extension.
Disease progression in both trials was assessed using the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score, a widely used measure of cognitive and functional decline in AD clinical trials. Disappointingly, the data presented at CTAD showed that semaglutide did not demonstrate a statistically significant slowing of disease progression compared with placebo on the CDR-SB primary endpoint in either trial. Similarly, analyses of secondary cognitive and functional outcomes did not reveal meaningful differences between treatment and placebo groups, indicating no clinically significant benefit in cognition or daily functioning over the primary treatment period. Despite the absence of efficacy on clinical endpoints, the trials reported biomarker changes consistent with semaglutide’s hypothesised biological effects.
Reductions of up to approximately 10% were observed in certain biomarkers, although these effects did not translate into measurable clinical benefit within the trial timeframe. Safety and tolerability in the AD population were consistent with the known profile of semaglutide in other indications, with adverse events such as gastrointestinal symptoms and weight loss reflecting its established effects. In a press release published just before CTAD, Novo Nordisk, the company developing semaglutide, announced the discontinuation of the 1-year extension period in the evoke and evoke+ trials, based on the efficacy results observed in the overall study population.