To test the therapeutic efficacy and safety of the GLP-1 agonist liraglutide in patients with idiopathic PD.

Insulin resistance (IR) is a promising therapeutic target in Parkinson’s disease (PD). Currently, receptor agonists of glucagon-like peptide 1 (GLP-1) are the safest and most reliable means of reducing IR. Liraglutide is a powerful GLP-1 agonist currently approved for treatment of diabetes and obesity.

In this single-center, randomized, double-blind, placebo-controlled trial, PD patients received, in addition to regular medications, once-daily self-administered injections of liraglutide (1.2 or 1.8 mg, as tolerated) or placebo in a 2:1 study design for 52 weeks after titration. Primary outcomes included the adjusted difference in the OFF-state Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part III, non-motor symptoms scale (NMSS) and Mattis Dementia Rating Scale (MDRS-2) at week 54. Efficacy analyses included patients who completed any post-randomization follow-up assessment.

63 patients were enrolled and randomized to liraglutide (n=42) or placebo (n=21). Twelve patients were early withdrawals, 4 of whom completed week 28 evaluation. Primary analysis included 37 active and 18 placebo subjects. At 54 weeks, NMSS scores had improved by 6.6 points in the liraglutide group and worsened by 6.5 points in the placebo group, a 13.1 point adjusted mean difference (p=0.07). MDS-UPDRS part III and MDRS-2 score changes from baseline did not significantly differ between active and placebo. Secondary outcome analysis revealed a significant improvement in MDS-UPDRS part-II scores in the treatment group (-4.1 points, p=0.001). Injection site reactions and gastrointestinal symptoms were common AEs. Eleven serious AEs were reported, none of which related to the study intervention.

Treatment with liraglutide improves critical features of PD, including non-motor symptoms and activities of daily living. These results validate similar outcomes reported with other GLP-1 agonists in PD and offer new strategies to treat the constellation of PD symptoms.