GLP-1 Add-On Therapy for Early PD Slows Disease Progression with Significant GI Side Effects

Results of a phase 2 clinical trial (NCT03439943) demonstrated that add-on treatment with Adlyxin (lixisenatide; Sanofi, Bridgewater, NJ), a glucagon-like peptide 1 (GLP-1) receptor agonist approved by the Food and Drug Administration for the treatment of type 2 diabetes, slowed disease progression in terms of motor disability in individuals with early Parkinson disease (PD). A significant percentage of individuals treated with Adlyxin reported gastrointestinal side effects: with 46% reporting nausea and 13% reporting vomiting.

The randomized, double-blind, multicenter, controlled trial included 156 participants aged 40-75 years who had been diagnosed with PD within the past 3 years and were on stable symptomatic medications. Participants were randomly assigned 1:1 to receive either daily subcutaneous Adlyxin or placebo for 12 months, followed by a 2-month washout period. The primary endpoint was the change from baseline in scores on the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III.

• At 12 months, MDS-UPDRS part III scores improved (change of -0.04 points) in the Adlyxin group and worsened (change of 3.04 points) in the placebo group (difference, 3.08; 95% CI, 0.86 to 5.30; P=.007).
• At 14 months, after a 2-month washout period, mean MDS-UPDRS motor scores in the off-medication state were 17.7 (95% CI, 15.7 to 19.7) in the Adlyxin group and 20.6 (95% CI, 18.5 to 22.8) in the placebo group.
• Secondary endpoint results did not differ substantially between the Adlyxin and placebo groups.
• There was a higher incidence of gastrointestinal side effects, including nausea and vomiting in the Adlyxin group (46% and 13% respectively) versus the placebo group (12% and 3% respectively).

A limitation of the study is that it took place over a period of ~1 year and only included individuals with early PD. Longer, larger trials are needed to determine the safety and efficacy of Adlyxin in people with PD.