The Zanos lab has recently published a preprint study examining the comparative effectiveness of diabetes medications in potentially reducing Alzheimer’s disease risk. The research was led by senior researchers Dr. Andrea Georgiou and Dr. Anna Onisiforou, key members of the Zanos laboratory team.

The study, titled “Metformin Shows Greater Potential Than Semaglutide in Reducing Alzheimer’s Risk in Diabetes Type II via Dual Actions: Tackling Disease Pathways and Environmental Herpesvirus Triggers,” employs an innovative multi-faceted approach combining network pharmacology, Mendelian Randomization analysis, and transcriptomic validation to evaluate 39 different diabetes treatments.

The team’s research reveals that metformin—one of the oldest and most widely prescribed diabetes medications—demonstrates superior potential for Alzheimer’s prevention compared to newer, high-profile medications like semaglutide (known commercially as Ozempic or Wegovy). This finding challenges assumptions that newer diabetes treatments would necessarily provide better neuroprotection.

Key findings from the Zanos lab show that metformin works through multiple mechanisms:

• Activation of AMPK, insulin, and adipocytokine signaling pathways that regulate critical Alzheimer’s-related processes
• Potential indirect effects against herpesviruses, which are emerging as possible environmental contributors to Alzheimer’s disease

These results suggest we should reconsider how we approach Alzheimer’s prevention in diabetes patients. While semaglutide has received significant attention for its effects on weight loss, our data indicates it has minimal engagement with the core neurodegenerative pathways connecting diabetes and Alzheimer’s disease.

The study also identified several dual-action therapies with efficacy comparable to metformin, supporting the need for personalized approaches to treatment selection based on individual risk profiles.

This research represents an important step toward developing targeted prevention strategies for the growing population of diabetes patients at elevated risk of developing Alzheimer’s disease. We are now working to validate these findings through clinical investigations focused specifically on high-risk populations.

The preprint is available at: https://doi.org/10.1101/2025.03.14.643306