In a 52-week phase 2b trial, liraglutide did not significantly improve brain glucose metabolism in Alzheimer's patients, but showed cognitive benefits on executive function measures.
Cognitive benefit p=0.01Executive function (ADAS-Exec) significantly improved with liraglutide despite the primary brain metabolism endpoint not reaching significance
What the researchers found
Primary outcome (cerebral glucose metabolic rate) showed no significant change (difference -0.17, p=0.14). Secondary outcome ADAS-Exec favored liraglutide (0.15, p=0.01). Safety was confirmed in non-diabetic AD patients.
Why it matters
This is the largest and most rigorous GLP-1 drug trial for Alzheimer's to date. While the primary endpoint was missed, the cognitive benefit signal supports continued investigation of GLP-1 drugs for AD.
How the study worked
Multicenter, randomized, double-blind, placebo-controlled phase 2b trial (ELAD, NCT01843075) with 204 participants receiving daily liraglutide or placebo for 52 weeks, with FDG-PET, MRI, and neuropsychometric assessments.
What this study cannot tell us
Missed primary endpoint. Secondary cognitive benefit was on a single measure. 52 weeks may be too short to detect meaningful changes in brain metabolism. 204 patients may be underpowered for some endpoints.
How to read the evidence
Phase 2b RCT — the gold standard design, but with a missed primary endpoint. The cognitive benefit is encouraging but requires confirmation in larger trials.
When this study was published
Published in 2025, reporting results of a trial registered as NCT01843075.
The bigger picture
Despite missing the primary endpoint, the executive function improvement adds to the evidence that GLP-1 drugs may benefit cognition in Alzheimer's. This trial will inform design of larger phase 3 studies.
Questions still open
- Would a longer treatment duration (>52 weeks) show brain metabolism changes?
- Should phase 3 trials use executive function as a primary endpoint?
- Would higher GLP-1 doses or newer agents like semaglutide produce stronger effects?
Common questions
Can liraglutide treat Alzheimer's disease?
Is it safe for Alzheimer's patients without diabetes?
Read the original research
Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial.
Nature medicine, 32(1), 353-361
Citation
Edison, Paul; Femminella, Grazia Daniela; Ritchie, Craig; Nowell, Joseph; Holmes, Clive; Walker, Zuzana; Ridha, Basil; Raza, Sanara; Livingston, Nicholas R; Frangou, Eleni; Love, Sharon; Williams, Gareth; Lawrence, Robert; Mcfarlane, Brady; Archer, Hilary; Coulthard, Elizabeth; Underwood, Benjamin R; Koranteng, Paul; Karim, Salman; Bannister, Carol; Perneczky, Robert; Prasanna, Aparna; Junaid, Kehinde; McGuinness, Bernadette; Nilforooshan, Ramin; Macharouthu, Ajay; Donaldson, Andrew; Thacker, Simon; Russell, Gregor; Malik, Naghma; Mate, Vandana; Knight, Lucy; Kshemendran, Sajeev; Holscher, Christian; Mansouri, Anita; Chester-Jones, Mae; Holmes, Jane; Tan, Trisha; Williams, Steve; Ashraf, Azhaar; Brooks, David J; Harrison, John; Hinz, Rainer; Tadros, George; Passmore, Anthony Peter; Ballard, Clive. (2026). Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial.. Nature medicine, 32(1), 353-361. https://doi.org/10.1038/s41591-025-04106-7