Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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 .
Source: Nature Medicine
Authors: Paul Edison, Grazia Daniela Femminella, Craig Ritchie, Joseph Nowell, Clive Holmes, Zuzana Walker, Basil Ridha, Sanara Raza, Nicholas R. Livingston, Eleni Frangou, Sharon Love, Gareth Williams, Robert Lawrence, Brady Mcfarlane, Hilary Archer, Elizabeth Coulthard, Benjamin R. Underwood, Paul Koranteng, Salman Karim, Carol Bannister, Robert Perneczky, Aparna Prasanna, Kehinde Junaid, Bernadette McGuinness, Ramin Nilforooshan, Ajay Macharouthu, Andrew Donaldson, Simon Thacker, Gregor Russell, Naghma Malik, Vandana Mate, Lucy Knight, Sajeev Kshemendran, Christian Holscher, Anita Mansouri, Mae Chester-Jones, Jane Holmes, Trisha Tan, Steve Williams, Azhaar Ashraf, David J. Brooks, John Harrison, Rainer Hinz, George Tadros, Anthony Peter Passmore, Clive Ballard
Institutions: Imperial College London, Cardiff University, Southern Health NHS Foundation Trust, University College London, Brighton and Sussex University Hospitals NHS Trust, MRC Clinical Trials Unit at UCL, King's College London, South West London and St George's Mental Health NHS Trust, North Bristol NHS Trust, University of Bristol, University of Cambridge, Northamptonshire Healthcare NHS Foundation Trust, Lancashire Care NHS Foundation Trust, Black Country Partnership NHS Foundation Trust, Nottinghamshire Healthcare NHS Foundation Trust, Queen's University Belfast, Surrey and Borders Partnership NHS Foundation Trust, NHS Ayrshire and Arran, NHS Lanarkshire, Bradford District Care NHS Foundation Trust, Cornwall Partnership NHS Foundation Trust, Somerset Partnership NHS Foundation Trust, Henan University of Traditional Chinese Medicine, University of Oxford, Aarhus University, Newcastle University, Amsterdam University Medical Centers, University of Manchester, Aston University, University of Exeter
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Award: G5806135073
OpenAlex ID: W4416850431