Novo Nordisk today announced disappointing topline results for two clinical trials, EVOKE and EVOKE+, of their GLP-1 agonist semaglutide for Alzheimer’s disease. Semaglutide is approved for treatment of diabetes and obesity and there were mixed signals in the literature for this drug and other drugs like it as to whether they could offer benefit to people with Alzheimer’s disease.
The 18-month trials included a combined 3808 participants, suggesting they should have been well-powered to show a benefit of treatment if one existed. The press release indicates that effects of treatment were observed on Alzheimer’s biomarkers, but it doesn’t say which ones. A more complete description of the results is anticipated to be presented at the upcoming Clinical Trials in Alzheimer’s Disease conference in December.
Some key facts are worth reminding. A clinical trial should answer a specific question. In this case, the answer to the question of can “semaglutatide provide benefit to people with mild Alzheimer’s dementia over 18 months of treatment” seems to be “No.” We don’t know the answer to similar questions about longer treatment, starting treatment earlier, or other GLP-1 drugs. Still, a key missing element is a strong therapeutic hypothesis to test for these drugs. They may have anti-inflammatory effects or improve vascular health, but the direct relationship to Alzheimer’s disease remains unclear. Hopefully the presentation in December will provide more clarity and give the field a better sense about whether these drugs should continue to be studied for a potential role in treating or preventing Alzheimer’s disease.
