Diego Bellido
Head of the Endocrinology and Nutrition Department at the Ferrol Hospital Complex (CHUF) and President of the Spanish Society for Obesity (SEEDO)
Does the press release accurately reflect the study?
“Yes, in essence it does. It correctly conveys that oral semaglutide did not slow the clinical progression of early Alzheimer’s, although there were changes in biomarkers that did not translate into clinical benefit. The potential bias lies in oversimplifying these nuances.”
Is the study of good quality?
“Yes. It is a methodologically robust piece of work: two phase 3 trials, randomized, double-blind, placebo-controlled, with 3,808 participants across 566 centers in 40 countries. The main conclusion is well supported because the primary endpoint was clearly negative in both trials.”
How does this work fit with the existing evidence?
“It fits as a study that tempers previous enthusiasm. Preclinical and observational evidence, as well as some small studies, suggested potential benefits of GLP-1 agonists, but this large trial does not confirm clinical efficacy in early Alzheimer’s.”
Have the authors taken confounding factors into account? Are there important limitations?
“Yes, reasonably so. They adjusted for relevant variables in the analysis and the design was solid. Still, there are limitations: higher dropout rates due to adverse effects in the semaglutide group, possible unblinding due to gastrointestinal side effects and weight loss, and the cerebrospinal fluid (CSF) sub-study was much smaller than the main trial.”
What are the real-world implications?
“The practical implication is clear: these data do not support using 14 mg oral semaglutide to slow early Alzheimer’s. It may still be useful for obesity or diabetes, but its benefits should not be extrapolated to disease-modifying treatment for Alzheimer’s.”