What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson's Disease: A Post Hoc Analysis.

Background: Exenatide is a GLP-1 receptor agonist that was recently studied for potential disease-modifying effects in a randomised, placebo-controlled clinical trial in patients with moderate stage Parkinson's disease, and showed positive effects on the motor severity of the disease which were sustained 12 weeks beyond the period of exenatide exposure. Analysis of pre-defined secondary outcomes revealed no statistically significant differences between patients treated with exenatide in total non-motor symptom burden and overall quality of life measures. Objective: The response of individual non-motor symptoms to an intervention may vary and thus this post hoc analysis was conducted to explore the possible effects of exenatide compared to placebo on individual non-motor symptoms. Results: Compared to placebo, patients treated with exenatide-once weekly had greater improvements in individual domains assessing mood/depression across all observer-rated outcome measures after 48 weeks including the "mood/apathy" domain of the NMSS, -3.3 points (95% CI -6.2, -0.4), p = 0.026; the "mood" score (Q1.3+Q1.4 of the MDS-UPDRS Part 1), -0.3 points (95% CI -0.6, -0.1), p = 0.034; and a trend in the MADRS total score, -1.7 points (95% CI -3.6, 0.2), p = 0.071. In addition, there was an improvement in the "emotional well-being" domain of the PDQ-39 of 5.7 points ((95% CI -11.3, -0.1), p = 0.047 though these improvements were not sustained 12 weeks after exenatide withdrawal. At 48 weeks these changes were of a magnitude that would be subjectively meaningful to patients and were not associated with changes in motor severity or other factors, suggesting exenatide may exert independent effects on mood dysfunction. Conclusions: These exploratory findings will contribute to the design of future trials to confirm the extent of motor and non-motor symptom effects of exenatide in larger cohorts of patients.