Are glucagon-like peptide-1 (GLP-1) receptor agonists useful in treating Parkinson's disease (PD)? Does the clinical trial with lixisenatide add anything?

Introduction: Parkinson's disease (PD) is a common neurodegenerative disease. Glucagon-like peptide-1 (GLP-1) receptor agonists decrease the incidence of developing PD and are being considered for the treatment of PD.

Areas covered: A phase 2 clinical trial of lixisenatide, a GLP-1 receptor agonist, in the early stages of PD. The primary endpoint was the MDS-UPDRS part 3 motor changes in score from baseline to 12 months in the on-medication state, and this was improved by lixisenatide. Post hoc subgroup analysis suggested that this effect of lixisenatide was greater in the <60-year-olds than in the ≥60 years. None of the secondary/exploratory mostly non-motor endpoints were significantly altered by lixisenatide.

Expert opinion: Although the scores between lixisenatide and placebo were statistically significantly different, the difference did not quite reach clinical significance. Lixisenatide, like exenatide, had no effect on the primary or secondary endpoints at 6 months suggesting that any benefits with GLP-1 receptor agonists in PD require long-term treatment. The apparent differences in the two age groups may be due to the bigger deterioration of motor scores in the <60-year-old group. Lixisenatide has promise but does not answer the discussion on GLP-1 receptor agonist treatment for PD.