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Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials
Jeffrey L Cummings, Alireza Atri, Mary Sano, Henrik Zetterberg, Philip Scheltens, Filip K Knop, Peter Johannsen, Christian Ahmad Wichmann et al.. The Lancet, 2026-03-19
Topic: Amyloid, tau and blood-test diagnosis
Between May 18, 2021, and Sept 8, 2023, 9981 participants were screened, of whom 3808 were randomly assigned; 1855 in evoke (semaglutide, n=928; placebo, n=927) and 1953 in evoke+ (semaglutide, n=976; placebo, n=977). Mean age was 72·2 years (SD 7·1), and mean CDR-SB score was 3·7 (SD 1·6) at baseline. In evoke+, 54 (2·8%) participants had small vessel pathology. In evoke and evoke+, mean changes in CDR-SB score from baseline to week 104 were 2·3 (SE 0·1) and 2·2 (0·1) with semaglutide, compared with 2·3 (0·1) and 2·1 (0·1) with placebo (estimated difference -0·08 [95% CI -0·35 to 0·20], p=0·57 in evoke and 0·10 [-0·17 to 0·38], p=0·46 in evoke+). Treatment-emergent adverse events were reported in 1729 (91·2%) of 1896 participants receiving semaglutide versus 1613 (84·8%) of 1902 receiving placebo. There were five fatalities considered treatment-related by the investigators (one in the semaglutide group and four in the placebo group). Oral semaglutide was not efficacious in slowing clinical progression in participants with early Alzheimer's disease. Safety and tolerability of semaglutide in early Alzheimer's disease is consistent with studies in other indications. FUNDING: Novo Nordisk.
Key findings
- Between May 18, 2021, and Sept 8, 2023, 9981 participants were screened, of whom 3808 were randomly assigned; 1855 in evoke (semaglutide, n=928; placebo, n=927) and 1953 in evoke+ (semaglutide, n=976; placebo, n=977).
- Mean age was 72·2 years (SD 7·1), and mean CDR-SB score was 3·7 (SD 1·6) at baseline.
- In evoke+, 54 (2·8%) participants had small vessel pathology.
- In evoke and evoke+, mean changes in CDR-SB score from baseline to week 104 were 2·3 (SE 0·1) and 2·2 (0·1) with semaglutide, compared with 2·3 (0·1) and 2·1 (0·1) with placebo (estimated difference -0·08 [95% CI -0·35 to 0·20], p=0·57 in evoke and 0·10 [-0·17 to 0·38], p=0·46 in evoke+).
- Treatment-emergent adverse events were reported in 1729 (91·2%) of 1896 participants receiving semaglutide versus 1613 (84·8%) of 1902 receiving placebo.
Why it matters
In two phase 3 randomized placebo-controlled trials with 3,808 participants, oral semaglutide 14 mg did not slow clinical progression in early Alzheimer's disease, with no significant difference from placebo on CDR-SB at week 104. Safety and tolerability were consistent with studies in other conditions, so this treatment was not efficacious for slowing early Alzheimer's disease.
Study details
- Study designclinical trial
- Participants928
- Evidence strengthHigh
How this study scored 72/100
Published in a top-tier journal. Scored zero for study design and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (The Lancet) |
| Journal's citation record | 4 / 4 | The Lancet: journal h-index 1,205 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 928 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 4 / 7 | Cited 73 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 36.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 6 / 6 | Cited 302.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 73 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Howard Feldman: h-index 105 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41865758) |
| Free to read | 2 / 2 | Free to read |
| Total | 72 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Cummings, J. L., Atri, A., Sano, M., Zetterberg, H., Scheltens, P., Knop, F. K., et al. (2026). Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. The Lancet. https://doi.org/10.1016/s0140-6736(26)00459-9
Vancouver
Cummings JL, Atri A, Sano M, Zetterberg H, Scheltens P, Knop FK, et al. Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. The Lancet. 2026. doi:10.1016/s0140-6736(26)00459-9. PMID: 41865758.
BibTeX
@article{cummings2026-41865758,
author = {Cummings, Jeffrey L and Atri, Alireza and Sano, Mary and Zetterberg, Henrik and Scheltens, Philip and Knop, Filip K and Johannsen, Peter and Wichmann, Christian Ahmad and others},
title = {{Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials}},
journal = {The Lancet},
year = {2026},
doi = {10.1016/s0140-6736(26)00459-9},
pmid = {41865758},
url = {https://doi.org/10.1016/s0140-6736(26)00459-9}
}
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