{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:50:19Z","timestamp":1790801419240,"version":"4.1.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Semaglutide is a glucagon-like peptide-1 analog that is on the market to treat type 2 diabetes and weight loss (Ozempic, Wegovy). Two phase 3 clinical trials have been conducted, Evoke and Evoke+, testing the drug in patients with Alzheimer's disease. The trial management presented results of the intermediate readout at week 104 of the CDR-SB scores, which were negative. On the basis of that, the management decided to declare the trials a failure. However, data from week 130 and 156 had not been statistically analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>When evaluating time points 130 and 156, several results show a separation between drug group and placebo group with semaglutide showing better results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the means, converting the SEMs to SDs and numbers of patients per group, I analyzed the results using the Welch T-test (two-tailed), which does not assume equal SD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The ADCS-ADL-MCI test, Evoke trial, week 130, did show a significant difference, p\u2009=\u20090.0039. Other test such as the ADAS-cog-13 results show trends towards improvement by semaglutide at week 156. Cerebrospinal fluid biomarker analyses showed significant differences in some AD markers, too.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results did show some limited drug effects at later time points of the trials. However, Semaglutide has been designed to stay in the blood for a long time and therefore does not cross the blood-brain barrier readily. Novel GLP-1 type drugs that can cross the blood-brain barrier easily may show superior protective effects in AD patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261458402","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:17:47Z","timestamp":1780996667000},"page":"1377-1381","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Semaglutide showed limited improvements in patients with Alzheimer's disease: Revisiting the evoke and evoke\u2009+\u2009clinical trials"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8159-3260","authenticated-orcid":false,"given":"Christian","family":"H\u00f6lscher","sequence":"first","affiliation":[{"name":"Shanxi Medical University"},{"name":"Kariya Pharmaceuticals Ltd, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.09.010"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-025-01226-z"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00155"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04106-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14313"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251351329"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01666-7"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(26)00459-9"},{"key":"e_1_3_3_10_2","volume-title":"Semaglutide concentration in cerebrospinal fluid from patients with early Alzheimer\u2019s disease after 12 weeks of subcutaneous treatment18th Clinical Trials on Alzheimer\u2019s Disease (CTAD)","author":"Johannsen P","unstructured":"Johannsen P, Bentsen M, Belmont-Rausch D, et al. Semaglutide concentration in cerebrospinal fluid from patients with early Alzheimer\u2019s disease after 12 weeks of subcutaneous treatment. In: 18th Clinical Trials on Alzheimer\u2019s Disease (CTAD), San Diego, CA, USA, 2025, abstract P091, December 1-4, 2025."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00726"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2018.1439014"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114187"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2023.2292461"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.02.012"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177972"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/1533317520953041"},{"key":"e_1_3_3_19_2","first-page":"7427136","article-title":"A dual GLP-1\/GIP receptor agonist is more effective than liraglutide in the A53\u2005T mouse model of Parkinson's disease","volume":"2023","author":"Zhang Z","year":"2023","unstructured":"Zhang Z, Shi M, Li Z, et al. A dual GLP-1\/GIP receptor agonist is more effective than liraglutide in the A53\u2005T mouse model of Parkinson's disease. Parkinsons Dis 2023; 2023: 7427136.","journal-title":"Parkinsons Dis"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1428817"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312323"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31585-4"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00378-2"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210256"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.03.024"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-191768"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261458402","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877261458402","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261458402","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:15:21Z","timestamp":1786378521000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877261458402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1177\/13872877261458402"],"URL":"https:\/\/doi.org\/10.1177\/13872877261458402","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}