Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2026 Jan;32(1):353-361.
doi: 10.1038/s41591-025-04106-7. Epub 2025 Dec 1.

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

Paul Edison  1   2 , Grazia Daniela Femminella  3 , Craig Ritchie  4 , Joseph Nowell  3 , Clive Holmes  5 , Zuzana Walker  6 , Basil Ridha  7 , Sanara Raza  3 , Nicholas R Livingston  3 , Eleni Frangou  8 , Sharon Love  8 , Gareth Williams  9 , Robert Lawrence  10 , Brady Mcfarlane  5 , Hilary Archer  11 , Elizabeth Coulthard  12 , Benjamin R Underwood  13 , Paul Koranteng  14 , Salman Karim  15 , Carol Bannister  9 , Robert Perneczky  3 , Aparna Prasanna  16 , Kehinde Junaid  17 , Bernadette McGuinness  18 , Ramin Nilforooshan  19 , Ajay Macharouthu  20 , Andrew Donaldson  21 , Simon Thacker  22 , Gregor Russell  23 , Naghma Malik  24 , Vandana Mate  25 , Lucy Knight  26 , Sajeev Kshemendran  27 , Christian Holscher  28 , Anita Mansouri  29 , Mae Chester-Jones  29 , Jane Holmes  29 , Trisha Tan  3 , Steve Williams  9 , Azhaar Ashraf  3 , David J Brooks  3   30   31 , John Harrison  9   32   33 , Rainer Hinz  34 , George Tadros  35 , Anthony Peter Passmore  18 , Clive Ballard  9   36
Affiliations
Clinical Trial

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

Paul Edison et al. Nat Med. 2026 Jan.

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 .

PubMed Disclaimer

Conflict of interest statement

Competing interests: P.E. was funded by the Medical Research Council and now by the Higher Education Funding Council for England (HEFCE). He has also received grants from Alzheimer’s Research UK, the Alzheimer’s Drug Discovery Foundation, Alzheimer’s Society UK, Novo Nordisk, GE Healthcare, AstraZeneca, Pfizer, Eli Lilly and Piramal Life Sciences. He has received speaker fees from Novo Nordisk, Pfizer, Nordea and Piramal Life Sciences. He has received educational and research grants from GE Healthcare, Novo Nordisk, Piramal Life Sciences/Life Molecular Imaging, Avid Radiopharmaceuticals and Eli Lilly. He was an external consultant to Novo Nordisk and has participated in their Scientific Advisory Board. He is a consultant to Roche, Pfizer and Biohaven. He is the director of Edison Health Sciences Ltd and Edison Sciences Limited. He is a member of the Scientific Advisory Board of CytoDyn and holds shares in CytoDyn. J. Harrison reports receipt of personal fees in the past 2 years from Actinogen, AlzeCure, Aptinyx, AstraZeneca, Athira Pharma, Axoltis, Axon Neuroscience, Bial Biotech, Biogen Idec, Boehringer Ingelheim, Brands2Life, Cerecin, Cognito, Cognition Therapeutics, Compass Pathways, Corlieve, Curasen, EIP Pharma, Eisai, GfHEU, Heptares, Impact, Ki Elements, LSP Operations, Lundbeck, Lysosomal Therapeutics, MyCognition, Neurotrack, the National Health Service, Novartis, Novo Nordisk, Nutricia, Probiodrug, Prothena, Recognify, Regeneron, reMYND, Roche, Signant, Syndesi Therapeutics, Takeda, Vivoryon Therapeutics and Winterlight Labs. Additionally, he holds stock options in Neurotrack and is a joint holder of patents with MyCognition, Ltd. B.R.U.ʼs position is partially funded by a donation from Gnodde Goldman Sachs Giving. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Consort diagram.
Study procedures: patient enrollment and randomization. PET, positron emission tomography.
Fig. 2
Fig. 2. Change in primary outcome (PET SUV) and sensitivity analyses (PET spectral) at 52 weeks.
(i) Figure shows change of scores at group level. Data are presented as mean ± s.e.m. (ii) Box plots show the median (center line) and interquartile range (IQR; box limits). Whiskers show the 95% confidence intervals (CIs), and points beyond this range are plotted as outliers. Individual data spread is plotted on the box-and-whiskers plot. Analysis of covariance adjusted for baseline values and stratification factors (age and MMSE) was used to compare between the placebo and treatment groups. Baseline n (placebo, 94; treatment, 93) and 52 weeks n (placebo, 82; treatment, 72) for PET SUV (a) and PET spectral (b). P values are unadjusted (P < 0.05).
Fig. 3
Fig. 3. Change in key secondary outcomes—ADAS-Exec, CDR-SoB and ADCS-ADL z-scores at 24 weeks and 52 weeks.
(i) Figure shows change of scores at group level. Data are presented as mean ± s.e.m. (ii) Box plots show the median (center line) and interquartile range (IQR; box limits). Whiskers show the 95% confidence intervals (CIs), and points beyond this range are plotted as outliers. Individual data spread is plotted on the box-and-whiskers plot. A multilevel mixed-effects model was used to compare between the placebo and liraglutide treatments. a, Baseline n (placebo, 100; treatment, 100), 24 weeks n (placebo, 95; treatment, 83) and 52 weeks n (placebo, 87; treatment, 79) for ADAS-Exec. b, Baseline n (placebo, 100; treatment, 99), 24 weeks n (placebo, 89; treatment, 80) and 52 weeks n (placebo, 88; treatment, 79) for CDR-SoB. c, Baseline n (placebo, 100; treatment, 100), 24 weeks n (placebo, 94; treatment, 83) and 52 weeks n (placebo, 89; treatment, 80) for ADCS-ADL. P values are unadjusted (P < 0.05).
Fig. 4
Fig. 4. Changes in other secondary outcomes—MRI volumes at 52 weeks.
MRI analyses for composite region brain (a), ventricular (b), cingulate isthmus (c), temporal lobe (d), parietal lobe (e), frontoparietal lobe (f) and whole gray matter (g). (i) Figure shows change of scores at group level. Data are presented as mean ± s.e.m. (ii) Box plots show the median (center line) and interquartile range (IQR; box limits). Whiskers show the 95% confidence intervals (CIs), and points beyond this range are plotted as outliers. Individual data spread is plotted on the box-and-whiskers plot. Analysis of covariance adjusted for baseline values and stratification factors (age and MMSE) was used to compare between the placebo and treatment groups. Baseline n (placebo, 101; treatment, 101) and 52 weeks n (placebo, 83; treatment, 75). P values are unadjusted (P < 0.05). A predefined P < 0.01 was used.
Fig. 5
Fig. 5. Changes in exploratory outcomes—VBM analyses at 52 weeks.
Panel a shows reduced voxel-wise decline of gray matter VBM in participants treated with liraglutide. VBM analyses are reported for frontal lobe (b), hippocampus (c), medial temporal lobe (d), parietal lobe (e), temporal lobe (f), whole gray matter (g) and whole white matter (h). (i) Figure shows change of scores at 52 weeks at the group level. Data are presented as mean ± s.e.m. (ii) Box plots show the median (center line) and interquartile range (IQR; box limits). Whiskers show the 95% confidence intervals (CIs), and points beyond this range are plotted as outliers. Individual data spread is plotted on the box-and-whiskers plot. Analysis of covariance adjusted for baseline values and stratification factors (age and MMSE) was used to compare between the placebo and liraglutide treatments. Baseline n (placebo, 101; treatment, 101) and 52 weeks n (placebo, 83; treatment, 75). P values are unadjusted (P < 0.05).
See this image and copyright information in PMC

References

    1. Aroda, V. R. A review of GLP-1 receptor agonists: evolution and advancement, through the lens of randomised controlled trials. Diabetes Obes. Metab.20, 22–33 (2018). - PubMed
    1. Qi, L. et al. Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced alzheimer disease mouse model. Eur. J. Pharmacol.783, 23–32 (2016). - PubMed
    1. Yang, Y. et al. Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats. Mol. Med. Rep.18, 2449–2457 (2018). - PubMed
    1. Duarte, A. I. et al. Liraglutide protects against brain amyloid-β1−42 accumulation in female mice with early Alzheimer’s disease-like pathology by partially rescuing oxidative/nitrosative stress and inflammation. Int. J. Mol. Sci.21, 1746 (2020). - PMC - PubMed
    1. Parthsarathy, V. & Holscher, C. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLoS ONE8, e58784 (2013). - PMC - PubMed

Publication types

MeSH terms

Associated data