Nat MedBrain & NeurologicalRCTDecember 1, 2025

Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial.

Edison P, Femminella GD, Ritchie C, Nowell J, Holmes C, Walker Z, Ridha B, Raza S, Livingston NR, Frangou E, Love S, Williams G, Lawrence R, Mcfarlane B, Archer H, Coulthard E, Underwood BR, Koranteng P, Karim S, Bannister C, Perneczky R, Prasanna A, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Holscher C, Mansouri A, Chester-Jones M, Holmes J, Tan T, Williams S, Ashraf A, Brooks DJ, Harrison J, Hinz R, Tadros G, Passmore AP, Ballard C

View on PubMed DOI: 10.1038/s41591-025-04106-7

Key Finding

Liraglutide, a diabetes drug, showed no effect on brain metabolism in Alzheimer's patients but improved executive function scores by a small but statistically significant amount over 52 weeks.

What This Study Found

Think of your brain as a city with different neighborhoods - some handling memory, others managing executive functions like planning and problem-solving. Researchers tested whether liraglutide, a diabetes medication that acts like a brain growth factor, could help 204 people with mild to moderate Alzheimer's disease. They were like urban planners checking if this drug could boost the city's overall energy consumption (measured by glucose metabolism) and improve how well different neighborhoods function. After a full year of daily injections, the drug didn't increase the brain's overall energy usage - the metabolic 'lights' stayed dim. However, there was a glimmer of hope in the executive function neighborhood, where patients on liraglutide scored slightly better on planning and problem-solving tests compared to those on placebo. It's like finding that while the whole city didn't get brighter, one important district showed signs of better organization.

Statistics Decoded

Primary outcome P=0.14: This means there's a 14% chance these brain metabolism results were just luck - not quite convincing enough (we usually want less than 5%). Executive function improvement P=0.01: This probably wasn't just chance - like flipping heads 99 times out of 100. The confidence intervals tell us the range where the real effect likely lies. For daily living activities (P=0.65) and overall dementia severity (P=0.81), the differences were likely just random noise - like differences you'd see between any two groups.

Why This Matters

This study suggests that repurposing diabetes drugs for Alzheimer's might have some benefit for thinking skills, but won't dramatically slow the disease's progression - important for setting realistic expectations for patients and families considering this treatment approach.

Original Abstract

Liraglutide, a glucagon-like peptide 1 (GLP-1) agonist and antidiabetic drug, has shown neuroprotective effects in animal models. In this study, we aimed to evaluate the safety and efficacy of liraglutide in mild to moderate Alzheimer's disease syndrome. 'Evaluating liraglutide in Alzheimer's disease' (ELAD) is a multicenter, randomized, double-blind, placebo-controlled phase 2b trial in 204 participants with mild to moderate Alzheimer's disease syndrome with no diabetes. Participants received daily injections of liraglutide or placebo for 52 weeks. They underwent fluorodeoxyglucose positron emission tomography, magnetic resonance imaging and detailed neuropsychometric evaluations. The primary outcome was a change in cerebral glucose metabolic rate. Secondary outcomes were safety and tolerability and cognitive changes. The primary outcome showed no significant differences in cerebral glucose metabolism (difference = -0.17; 95% confidence interval: -0.39 to 0.06; P = 0.14) between the two groups. The secondary outcome-score on the Alzheimer's Disease Assessment Scale-Executive domain (ADAS-Exec)-performed better in liraglutide-treated patients compared to placebo (0.15; 95% confidence interval: 0.03-0.28; unadjusted P = 0.01). No significant differences were observed in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (-0.58; 95% confidence interval: -3.13 to 1.97; unadjusted P = 0.65) or Clinical Dementia Rating-Sum of Boxes (CDR-SoB) (-0.06; 95% confidence interval: -0.57 to 0.44; unadjusted P = 0.81) scores. Liraglutide was generally safe and well tolerated in non-diabetic patients with Alzheimer's disease. ClinicalTrials.gov identifier: NCT01843075 .