by Isabella Colonna
For March we have selected: Vijiaratnam N, Girges C, Auld G, McComish R, King A, Skene SS, Hibbert S, Wong A, Melander S, Gibson R, Matthews H, Dickson J, Carroll C, Patrick A, Inches J, Silverdale M, Blackledge B, Whiston J, Hu M, Welch J, Duncan G, Power K, Gallen S, Kerr J, Chaudhuri KR, Batzu L, Rota S, Jabbari E, Morris H, Limousin P, Greig N, Li Y, Libri V, Gandhi S, Athauda D, Chowdhury K, Foltynie T. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson’s disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. Lancet. 2025 Feb 22;405(10479):627-636. doi: 10.1016/S0140-6736(24)02808-3. Epub 2025 Feb 4. PMID: 39919773.
The treatment of Parkinson’s disease currently relies on symptomatic therapies, while disease-modifying treatments remain a key priority for the future. Exenatide, a GLP-1 receptor agonist used for type 2 diabetes, has demonstrated neuroprotective effects in preclinical studies involving both toxin-induced and genetic animal models of Parkinson’s disease.
This phase 3 multicentre, double-blind, randomised trial investigates whether treatment with exenatide can slow the progression of Parkinson’s disease. A total of 194 participants diagnosed with Parkinson’s disease were enrolled and randomly assigned (1:1) to receive either a 2mg extended-release exenatide subcutaneous injection once per week (n=97) or a visually identical placebo (n=97) for 96 weeks. The primary outcome was the OFF-medication score on Part III of the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) at 96 weeks. Secondary outcomes included additional clinical measures and radiological assessments, such as changes in the striatal binding ratio on DaT-SPECT between baseline and week 96. At the end of the treatment period, no significant differences were observed between the exenatide and placebo groups in either the primary or secondary outcomes. Exenatide was well tolerated and demonstrated a favourable safety profile, with 10 serious adverse events reported in the treatment group compared to 12 in the placebo group.
In contrast to previous trial results, this study found no clinical benefit of administering 2mg extended-release exenatide subcutaneously once per week compared to placebo.
