Landmark 310 · Trial in people
Stockholm exenatide trial
Brain scans changed, but movement scores did not, in 59 people. This matches the larger UK trial.
In short
A 59-person Swedish Phase 2 found exenatide shifted brain metabolic networks on PET scans but gave no movement benefit, matching the UK Phase 3.
- What it is
- Trial in people
- Outcome
- Did not work
- When
- 2020–2025
- Size
- 59 people · Phase 2
- Approach
- Look beyond the brain
- Research lane
- Metabolic drug repurposing
- Trial registry
- NCT04305002
- Last checked
- 19 Oct 2026
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
Per Svenningsson and colleagues, Center for Neurology, Stockholm, with Karolinska Institutet. David Eidelberg (Feinstein Institutes, New York) contributed the network analysis.
What happened
Exenatide is a GLP-1 diabetes drug. After the 2013 pilot (landmark 101), this trial (NCT04305002, Phase 2, started January 2020) asked a different question from the UK Phase 3 (landmark 142): does the drug change the brain's activity pattern? The primary outcome was FDG-PET network analysis (FDG-PET maps how much sugar each brain region uses).
Fifty-nine people with Parkinson's on levodopa were randomised; 55 were analysed (29 placebo, 26 exenatide). They had weekly exenatide 2 mg or placebo for 18 months, then a 3-month washout, with scans at baseline, 9 and 21 months. The results were presented at the 2025 international Movement Disorders congress:
- The motor-related brain pattern (PDRP) fell on exenatide and rose on placebo at 9 months (interaction p = 0.01), and differed between groups over 21 months (p = 0.01).
- A cognition-related pattern showed a 9-month difference (p < 0.05) that was not significant at 21 months (p = 0.11).
- Blood inflammatory and metabolic markers differed between groups.
- Motor scores (MDS-UPDRS Part 3, on and off medication) did not differ.
- The authors say the effects did not persist after stopping the drug.
Why it moved us toward a cure
It shows exenatide has a measurable biological effect on the brain, yet no clinical gain. That narrows the GLP-1 question: reaching the brain is not enough, or the imaging changes do not track the disease. Lixisenatide (landmark 141) remains the one positive GLP-1 result.
Outcome
Dead end for exenatide slowing symptoms. No peer-reviewed paper yet.
Sources
- Markaki et al., MDS Congress 2025 abstract
- NeurologyLive coverage, 28 Oct 2025
- ClinicalTrials.gov NCT04305002 (API, 19 Oct 2026)
- Not yet verified: the full paper; effect sizes and dropout reasons; the registry still says 60 enrolled and status "unknown"; the NeurologyLive article gives p = .001 for one result where the abstract gives p = 0.01 (abstract used here).
How it connects
Built on
- builds on Exenatide pilot · 2013
- responds to Exenatide Phase 3 (Exenatide-PD3) · 2025
Led to
None recorded.