Study wrapper · #1162
Semaglutide attenuates a proteomics-based dementia risk signature in older adults with overweight or obesity and cardiovascular disease without diabetes: A post hoc analysis of the SELECT phase 3 trial.
Editor's note
This is a post hoc biomarker analysis of a randomized trial, which places it above observational work but well below a dedicated dementia outcomes trial. The outcome measured is a proteomic risk score, so the finding is that semaglutide slowed movement of a predictive signature — not that anyone's cognitive trajectory was documented to change. The effect sizes are consistent across two time horizons and the sample is large, which makes the signal worth noting. The EVOKE trials, which measure clinical cognitive outcomes directly, remain the test that matters.
Plain-language abstract
Researchers went back to stored blood samples from SELECT, a large randomized trial of semaglutide 2.4 mg in adults with overweight or obesity and cardiovascular disease but no diabetes. In the 2,970 participants aged 65 and older, they applied a validated 25-protein blood score that estimates a person's 5-year and 20-year risk of dementia, comparing baseline with week 104. Over two years, the protein-based risk score rose less in the semaglutide group than in the placebo group — about 2.5-fold less increase in the 5-year estimate and 1.67-fold less in the 20-year estimate — and participants on semaglutide were 36% less likely to move into a higher risk category. The endpoint here is a blood-based risk signature, not diagnosed dementia.