GLP-1 Agonist Slows Brain Volume Loss and Cognitive Decline in People with Alzheimer Disease
Treatment for people with mild Alzheimer disease (AD) using liraglutide, a glucagon-like peptide 1 (GLP-1) agonist, was associated with slower brain volume loss and cognitive decline vs placebo. The results from a phase 2b clinical trial were presented at the 2024 meeting of the Alzheimer’s Association International Conference (AAIC).
The study included 204 participants with mild AD who were randomized to receive daily subcutaneous injections of liraglutide at 1.8 mg (n=102) or placebo (n=102). Participants were assessed using MRI brain scans for brain volume loss and PET scans for cerebral glucose metabolism rate change from baseline, along with testing for cognitive decline and memory loss.
Results for participants who remained in the study throughout the full 52-week duration (liraglutide, n=79; placebo, n=87) are as follows:
- Liraglutide-treated participants experienced 50% less brain volume loss compared with placebo-treated participants, particularly in the frontal, temporal, and parietal lobes, as well as in whole cortical grey matter.
- Liraglutide-treated participants experienced reduced cognitive decline by up to 18% compared with placebo-treated participants.
- The endpoint of cerebral glucose metabolism rate change in cortical regions of the brain was not met.
“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid-beta and tau, and improving how the brain’s nerve cells communicate,” said Paul Edison, MD, PhD, Presenting Author and Professor of Science at Imperial College London.
Dr. Edison receives funding from the Alzheimer’s Society, the Alzheimer’s Drug Discovery Foundation, Novo Nordisk, the John and Lucile Van Geest Foundation, and the National Institute for Health and Care Research (NIHR) Biomedical Research Center.