Exenatide and the treatment of patients with Parkinson's disease

J Clin Invest. 2013 Jun;123(6):2730-6. doi: 10.1172/JCI68295.


BACKGROUND. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. METHODS. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson's disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). RESULTS. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). CONCLUSION. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD.

Trial registration: Clinicaltrials.gov NCT01174810.

Funding: Cure Parkinson's Trust.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Constipation / chemically induced
  • Disease Progression
  • Drug Repositioning
  • Exenatide
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Motor Activity / drug effects
  • Off-Label Use
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Venoms / administration & dosage*
  • Venoms / adverse effects
  • Weight Loss / drug effects


  • Antiparkinson Agents
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Exenatide

Associated data

  • ClinicalTrials.gov/NCT01174810