The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial

James L Mitchell, Hannah S Lyons, Jessica K Walker, Andreas Yiangou, Olivia Grech, Zerin Alimajstorovic, Nigel H Greig, Yazhou Li, Georgios Tsermoulas, Kristian Brock, Susan P Mollan, Alexandra J Sinclair

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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.

Original languageEnglish
Pages (from-to)1821-1830
Number of pages10
Issue number5
Early online date13 Mar 2023
Publication statusPublished - 1 May 2023

Bibliographical note

© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.


  • Adult
  • Humans
  • Female
  • Young Adult
  • Exenatide
  • Pseudotumor Cerebri/drug therapy
  • Glucagon-Like Peptide-1 Receptor/agonists
  • Peptides
  • Venoms/therapeutic use
  • Hypoglycemic Agents/therapeutic use
  • Diabetes Mellitus, Type 2/drug therapy


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