Liraglutide in mild to moderate Alzheimer’s disease: a phase 2b clinical trial
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 .
Authors
- Elizabeth Coulthard (ORCID: https://orcid.org/0000-0002-0017-9595)
- Rainer Hinz (ORCID: https://orcid.org/0000-0002-7808-9207)
- Azhaar Ashraf (ORCID: https://orcid.org/0000-0002-7660-9432)
- Salman Karim (ORCID: https://orcid.org/0000-0002-4643-0677)
- Sanara Raza
- Nicholas R Livingston (ORCID: https://orcid.org/0000-0002-6582-2545)
- Robert Perneczky (ORCID: https://orcid.org/0000-0003-1981-7435)
- Tricia Tan (ORCID: https://orcid.org/0000-0001-5873-3432)
- Benjamin R. Underwood (ORCID: https://orcid.org/0000-0003-3427-9487)
- Sajeev Kshemendran
- Anita Mansouri
- Ramin Nilforooshan (ORCID: https://orcid.org/0000-0001-9801-183X)
- Basil H. Ridha (ORCID: https://orcid.org/0000-0002-8850-9922)
- Clive Ballard (ORCID: https://orcid.org/0000-0003-0022-5632)
- Craig Ritchie (ORCID: https://orcid.org/0000-0002-6202-6906)
- Paul Edison
- Paul Koranteng
- Steven Williams (ORCID: https://orcid.org/0000-0003-4299-1941)
- David J. Brooks (ORCID: https://orcid.org/0000-0003-2602-2518)
- Mae Chester‐Jones (ORCID: https://orcid.org/0000-0002-9710-5866)
- Bernadette McGuinness (ORCID: https://orcid.org/0000-0002-7028-5633)
- Grazia Daniela Femminella (ORCID: https://orcid.org/0000-0002-7397-483X)
- Sharon Love (ORCID: https://orcid.org/0000-0002-6695-5390)
- Andrew Donaldson (ORCID: https://orcid.org/0000-0003-0891-327X)
- John Harrison (ORCID: https://orcid.org/0000-0002-0225-4923)
- Jane Holmes (ORCID: https://orcid.org/0000-0001-7123-0004)
- Kehinde Junaid (ORCID: https://orcid.org/0000-0001-5986-395X)
- Brady McFarlane
- Naghma Malik
- George Tadros (ORCID: https://orcid.org/0000-0001-5820-7643)
- Clive Holmes (ORCID: https://orcid.org/0000-0003-1999-6912)
- Christian Hölscher (ORCID: https://orcid.org/0000-0002-8159-3260)
- Ajay Macharouthu (ORCID: https://orcid.org/0000-0001-5197-4727)
- Simon Thacker (ORCID: https://orcid.org/0000-0002-3203-1392)
- Zuzana Walker (ORCID: https://orcid.org/0000-0001-7346-8200)
- Eleni Frangou (ORCID: https://orcid.org/0000-0002-5978-292X)
- Gregor Russell (ORCID: https://orcid.org/0000-0001-9449-2824)
- Hilary Archer
- Vandana Mate
- Robert M. Lawrence
- Anthony Peter Passmore
- Carol Bannister
- Gareth Williams
- Aparna Prasanna
- Lucy Knight
- Joseph Nowell
Institutions
- Queen's University Belfast (GB)
- North Bristol NHS Trust (GB)
- Aston University (GB)
- King's College London (GB)
- Aarhus University (DK)
- University of Exeter (GB)
- University of Cambridge (GB)
- NHS Ayrshire and Arran (GB)
- South Essex Partnership University Foundation NHS Trust (GB)
- NHS Lanarkshire (GB)
- Southern Health NHS Foundation Trust (GB)
- Nottinghamshire Healthcare NHS Foundation Trust (GB)
- University of Manchester (GB)
- University of Bristol (GB)
- University of Oxford (GB)
- MRC Clinical Trials Unit at UCL (GB)
- South West London and St George's Mental Health NHS Trust (GB)
- North West Boroughs Healthcare NHS Foundation Trust (GB)
- Amsterdam Neuroscience (NL)
- NIHR Imperial Biomedical Research Centre (GB)
- Cambridge Cognition (United Kingdom) (GB)
- Northamptonshire Healthcare NHS Foundation Trust (GB)
- Bradford District Care NHS Foundation Trust (GB)
- Black Country Partnership NHS Foundation Trust (GB)
- Lancashire Care NHS Foundation Trust (GB)
- Cornwall Partnership NHS Foundation Trust (GB)
- University Hospitals Sussex NHS Foundation Trust (GB)
- Somerset Partnership NHS Foundation Trust (GB)
- First Affiliated Hospital of Henan University (CN)
- University College London (GB)
- Imperial College London (GB)
- Surrey and Borders Partnership NHS Foundation Trust (GB)
- Cardiff University (GB)
- Newcastle University (GB)
- University of Wales (GB)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1038/s41591-025-04106-7
- Citations
- 10
- Primary Topic
- Diabetes Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 12.95
Funders
- Alzheimer's Society
- National Institute for Health and Care Research
- Imperial College London
- King's College London
- Novo Nordisk
- NIHR Imperial Biomedical Research Centre