The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.
Author
Mitchell, James LLyons, Hannah S
Walker, Jessica K
Yiangou, Andreas
Grech, Olivia
Alimajstorovic, Zerin
Greig, Nigel H
Li, Yazhou
Tsermoulas, Georgios
Brock, Kristian
Mollan, Susan P
Sinclair, Alexandra J
Publication date
2023-05-02
Metadata
Show full item recordAbstract
Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks -5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.Citation
Mitchell JL, Lyons HS, Walker JK, Yiangou A, Grech O, Alimajstorovic Z, Greig NH, Li Y, Tsermoulas G, Brock K, Mollan SP, Sinclair AJ. The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial. Brain. 2023 May 2;146(5):1821-1830. doi: 10.1093/brain/awad003.Type
ArticleAdditional Links
https://academic.oup.com/brainPMID
36907221Journal
BrainPublisher
Oxford University Pressae974a485f413a2113503eed53cd6c53
10.1093/brain/awad003