Semaglutide Phase 2 trials (Oslo, MOST-ABLE)

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

Oslo University Hospital (semaglutide; principal investigator Vidar Gundersen); University of Osaka Hospital with eight Japanese sites (oral semaglutide, MOST-ABLE), funded by the Japan Agency for Medical Research and Development (AMED). Novo Nordisk supplied drug and placebo for MOST-ABLE.

What happened

GLP-1 drugs mimic a gut hormone. The 194-person exenatide Phase 3 found no benefit (landmark 142) while lixisenatide slowed motor decline by about 3 points over a year (landmark 141). The question is whether better brain-reaching drugs will do what exenatide did not. The registered semaglutide follow-ons are below. The slow-release exenatide PT320 and the Stockholm exenatide trial are in landmark 309 and landmark 310.

• Semaglutide, Oslo ("GLP1R in Parkinson's Disease", NCT03659682). Phase 2, randomised, quadruple-masked, delayed-start design: 1.0 mg semaglutide or placebo weekly by injection, main measure the off-medication motor score (MDS-UPDRS Part III) at 48 months. The registry lists 120 people (estimated), start January 2019 (estimated), end December 2024 (estimated). The record has not been updated since September 2018, when its status was "not yet recruiting" (now "unknown"). No results or publication found; I could not confirm it ever enrolled.
• Oral semaglutide, MOST-ABLE (jRCT2051230090). Phase 2, 99 people with Parkinson's (Hoehn and Yahr 1–2.5), 7 mg, 14 mg or placebo daily (1:1:1) for 36 weeks, then 12 weeks without drug. Recruited 6 November 2023 to 30 September 2024. Primary measure: change in off-state MDS-UPDRS Part III at 48 weeks. The protocol said data collection would finish by December 2025 and the study by March 2026, with an optional follow-up to November 2026; the registry now reads "not recruiting" (updated 2 December 2025). I found no results.
• Not found: no US or UK semaglutide Parkinson's trial turned up in registry searches. Separately, Novo Nordisk's two Phase 3 trials of oral semaglutide in early Alzheimer's (EVOKE and EVOKE+, 3,808 people) did not beat placebo on CDR-SB (trade-press reports of November 2025).

Why it moved us toward a cure

Semaglutide is a newer GLP-1 drug than exenatide, so these trials help decide whether the GLP-1 idea survives exenatide's Phase 3 failure (landmark 142), or whether lixisenatide (landmark 141) was a fluke. The Oslo trial is stalled with no news.

Outcome

Open, with no results for either semaglutide trial. The registry gaps are themselves a finding: years after the exenatide Phase 2, the follow-up evidence is thin.

Sources

• ClinicalTrials.gov NCT03659682 (via API, re-read 22 Oct 2026: status "unknown", no update since 6 Sep 2018, no sites listed)
• MOST-ABLE protocol, BMJ Open 2025;15:e112318, DOI 10.1136/bmjopen-2025-112318, PMID 41448692 · jRCT2051230090
• Alzforum: semaglutide · Patient Care Online, 24 Nov 2025, on EVOKE
• Not yet verified: whether the Oslo trial ever enrolled; any MOST-ABLE results; the EVOKE numbers beyond the trade press (Alzforum page not re-read).