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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, et al.. Nature Medicine, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
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 .
What this study adds
Evidence grade: Null result
The record lists 204 participants. In this phase 2b trial, liraglutide showed no significant difference in cerebral glucose metabolism, the primary outcome. Reported effect size: Cerebral glucose metabolism difference -0.17 (95% CI -0.39 to 0.06, p=0.14); CDR-SB -0.06 (95% CI -0.57 to 0.44).
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Edison, P., Femminella, G. D., Ritchie, C., Nowell, J., Holmes, C., Walker, Z., et al. (2025). Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial. Nature Medicine. https://doi.org/10.1038/s41591-025-04106-7
Vancouver
Edison P, Femminella GD, Ritchie C, Nowell J, Holmes C, Walker Z, et al. Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial. Nature Medicine. 2025. doi:10.1038/s41591-025-04106-7. PMID: 41326666.
BibTeX
@article{edison2025-41326666,
author = {Edison, P. and Femminella, G. D. and Ritchie, C. and Nowell, J. and Holmes, C. and Walker, Z. and Ridha, B. and Raza, S. and Livingston, N. R. and Frangou, E. and others},
title = {{Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial}},
journal = {Nature Medicine},
year = {2025},
doi = {10.1038/s41591-025-04106-7},
pmid = {41326666},
url = {https://doi.org/10.1038/s41591-025-04106-7}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- 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.
Why it matters
In this phase 2b trial, liraglutide showed no significant difference in cerebral glucose metabolism, the primary outcome. A secondary cognitive measure performed better in liraglutide-treated patients, but no significant differences were seen in activities of daily living.
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Study details
- Study designphase-2-trial
- Participants204
- Effect sizeCerebral glucose metabolism difference -0.17 (95% CI -0.39 to 0.06, p=0.14); CDR-SB -0.06 (95% CI -0.57 to 0.44)
- Evidence strengthNull-result
Limitations
Primary endpoint was a brain imaging biomarker rather than a clinical outcome; the positive cognitive signal was a secondary outcome with unadjusted p-value; 12-month duration; phase 2b size.
How this study scored 78/100
Published in a top-tier journal, and it is a mid-stage phase 2 trial. Scored zero for randomized / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 76 of the 98 points we could judge it on, which is 78 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 8 / 12 | A mid-stage phase 2 trial |
| Strength of evidence | 3 / 5 | Rated “null-result” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 204 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 68 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 37.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 3 / 4 | Cited 68 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Clive G. Ballard: h-index 141 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 30 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41326666) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 76 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 76 of the 98 points we could judge it on is 78 out of 100. |
| Total | 78 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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