Trial results for a Phase 3 study (NCT05891496) investigating semaglutide in people with Alzheimer's disease were posted on ClinicalTrials.gov on 2026-02-24. The study explored the effect of semaglutide on the immune system and other biological processes, showing a mean of 41.25 differentially expressed genes in cerebrospinal fluid (CSF) cells for the semaglutide group compared to 21.00 for placebo.
Background
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved in various countries for the treatment of type 2 diabetes and excess body weight. This particular study aimed to understand whether semaglutide could also be used for the treatment of Alzheimer's disease by investigating its effects on the immune system and other biological processes.
Trial design
The study (NCT05891496) was a Phase 3, randomized, placebo-controlled trial that enrolled 23 participants. The trial investigated semaglutide in individuals with Alzheimer's disease. Participants were randomized to receive either semaglutide or placebo. The study's objective was to understand how semaglutide affects the immune system and other biological processes in this population over approximately 77 weeks, with an initial 12-week treatment period.
Key results
The trial results provided insights into the biological effects of semaglutide and its safety profile in people with Alzheimer's disease. For the outcome of 'Change in Gene Expression Assessed by Single-cell Ribonucleic Acid Sequencing (scRNAseq) (Cells in Cerebrospinal Fluid [CSF])':
- The semaglutide group showed a mean of 41.25 differentially expressed genes (Standard Deviation: 29.68).
- The placebo group showed a mean of 21.00 differentially expressed genes (Standard Deviation: 25.70).
For the outcome of 'Change in Gene Expression Assessed by scRNAseq (Cells in Blood)':
- The semaglutide group showed a mean of 10.00 differentially expressed genes (Standard Deviation: 5.97).
- The placebo group showed a mean of 16.50 differentially expressed genes (Standard Deviation: 15.86).
Regarding safety, the 'Number of Treatment Emergent Adverse Events (TEAEs)' was:
- Semaglutide group: 31 events.
- Placebo group: 8 events.
What this means
This Phase 3 study provides initial data on the biological impact of semaglutide in people with Alzheimer's disease, specifically regarding gene expression changes in CSF and blood cells. The observed differences in differentially expressed genes between the semaglutide and placebo groups suggest that semaglutide influences immune system and other biological processes. However, the study did not report clinical efficacy endpoints for Alzheimer's disease. The higher number of Treatment Emergent Adverse Events in the semaglutide group compared to placebo warrants further investigation into the safety profile in this specific patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05891496, titled 'A Research Study Looking at the Effect of Semaglutide on the Immune System and Other Biological Processes in People With Alzheimer's Disease,' were posted on 2026-02-24 on clinicaltrials.gov.