Exenatide Phase 3 (Exenatide-PD3)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Nirosen Vijiaratnam, Tom Foltynie and colleagues at University College London and five other UK research hospitals (King's College Hospital was one). Funded by the NIHR and Cure Parkinson's. Published in The Lancet, February 2025.

What happened

The open-label pilot (landmark 101) and the 62-person placebo-controlled Phase 2 in 2017 (landmark 20) suggested exenatide, a diabetes injection, might slow Parkinson's. This trial was the large test.

• Design. Double-blind, placebo-controlled. 194 people (97 per arm), aged 25-80, Hoehn and Yahr stage 2.5 or less on dopamine treatment, randomised between January 2020 and April 2022 to extended-release exenatide 2 mg or matching placebo by weekly pen injection for 96 weeks (NCT04232969). Main measure: motor score off medication (MDS-UPDRS Part III). 92 exenatide and 96 placebo participants had a follow-up visit and were analysed.
• Result. At 96 weeks the score worsened by 5.7 points on exenatide and 4.5 on placebo; adjusted difference 0.92 (95% CI −1.56 to 3.39, p=0.47). Secondary outcomes also showed no benefit. Serious adverse events: 9% on exenatide, 11% on placebo. The authors wrote that they found no evidence to support exenatide as a disease-modifying treatment.
• Expression of concern (confirmed). The Lancet published "Expression of Concern: Exenatide once a week versus placebo..." by The Editors of the Lancet, online 22 June 2026, in the issue of 27 June 2026 (vol 407, issue 10548, p. 2588; DOI 10.1016/S0140-6736(26)01241-9; PMID 42330995). The earlier report that it appeared in July was wrong: The Limbic's article of 2 July came later. PubMed and Crossref confirm the notice and link it to the 2025 paper. The notice text was not readable here (publisher page blocked). Per The Limbic's account of it, a regulatory inspection of King's College Hospital, one of the sites, raised department-wide concerns about trial conduct, oversight and governance. The editors were waiting for the hospital's investigations and for an assessment of whether the findings could affect the data or conclusions, and said they would update the notice. The 2025 paper has not been retracted. A recheck on 23 Oct 2026 found no update, correction or retraction in PubMed or Europe PMC (the Lancet page itself was blocked, so a later update is not ruled out). Some sources give 18 May 2026 as a date; a forum post quoting the notice (not the notice itself) says that is when the Lancet was made aware of the inspection findings, not the date of the notice.
• Funder report (source sweep, Oct 2026). Cure Parkinson's reports funding a study of samples from this Phase 3 trial to understand how exenatide acts (contracted in the year to March 2025).

Why it moved us toward a cure

It showed that a positive Phase 2 does not guarantee a positive Phase 3, and it cooled the GLP-1 field, though not for every drug: exenatide reaches the brain poorly compared with some newer agents (lixisenatide, landmark 141). It also stands as a clean example of how motor-score trials can mislead.

Outcome

Dead end for exenatide in Parkinson's. The wider GLP-1 idea stays open on other drugs. If the concern at the one site changes the analysis, it would more likely reduce confidence in the result than overturn it, but that is not known.

Sources

• Vijiaratnam et al., Lancet 2025;405:627–636, DOI 10.1016/S0140-6736(24)02808-3 · PubMed 39919773
• ClinicalTrials.gov NCT04232969 · UCL news, Feb 2025
• Expression of concern, Lancet 2026;407:2588, DOI 10.1016/S0140-6736(26)01241-9 · PubMed 42330995
• The Limbic, 2 Jul 2026, on the notice's content (page blocked automated reading; text seen only in search summaries)
• Cure Parkinson's Impact Report 2025 (1 Apr 2024 to 31 Mar 2025)
• Not yet verified: the notice's full text (only its existence, date and title are confirmed from PubMed and Crossref; the wording of the concerns comes from The Limbic); any King's College Hospital statement; whether the notice was updated after 25 Jun 2026 (the PubMed record was last revised that day); how many of the 194 were enrolled at King's.