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A Phase II, Randomized, Double-Blinded, Placebo-Controlled Trial of Liraglutide in Parkinson's Disease

32 Pages Posted: 12 Sep 2022

See all articles by Elliot Hogg

Elliot Hogg

Cedars Sinai Medical Center - Department of Neurology

Tina Wu

Cedars Sinai Medical Center - Department of Neurology

Catherine Bresee

Cedars Sinai Medical Center - Biostatistics Core

Jeffrey Wertheimer

Cedars Sinai Medical Center - Department of Physical Medicine and Rehabilitation

Camille Malatt

Cedars Sinai Medical Center - Department of Neurology

Echo Tan

Cedars Sinai Medical Center - Department of Neurology

Hayley Pomeroy

Cedars Sinai Medical Center - Department of Neurology

Miriam Nuno

University of California, Davis - Department of Public Health Sciences

Richard Wyse

Cure Parkinson's

Michele Tagliati

Cedars Sinai Medical Center - Department of Neurology

More...

Abstract

Background: Metabolic disorders such as insulin resistance and diabetes are associated with Parkinson’s disease (PD). Therefore, the identification and repurposing of drugs already used to treat insulin resistance, like glucagon-like peptide-1 (GLP-1) agonists, is a promising treatment strategy for PD. Liraglutide is a powerful GLP-1 agonist, used in diabetes and obesity treatment.

Methods: In a single-center, randomized, double-blind, placebo-controlled trial, PD patients self-administered liraglutide injections once-daily (1.2 or 1.8 mg, as tolerated) or placebo in a 2:1 study design for 52 weeks after titration. Primary outcomes included adjusted difference in the OFF-state Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part III, non-motor symptom scale (NMSS) and Mattis Dementia Rating Scale (MDRS-2) at week 54. Secondary outcomes included global MDS-UPDRS scores and subscores, quality of life scores (Parkinson Disease Questionnaire, PDQ-39) and other neuropsychological tests. Efficacy analyses were based on an intention-to-treat and per-protocol design for patients completing post-randomization follow-up assessments.

Findings: Sixty-three subjects were enrolled and randomized to liraglutide (n=42) or placebo (n=21). There were 12 early withdrawals (9 liraglutide, 3 placebo), 4 of whom completed week 28 endpoint assessments. 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<0.05). MDS-UPDRS part III and MDRS-2 score changes did not significantly differ between liraglutide and placebo. Secondary outcome analyses revealed a significant improvement of MDS-UPDRS part II (p=0.001), PDQ-39 (p<0.001), and Parkinson's Anxiety Scale Avoidance Behavior scores (p<0.05) in the treatment group. MDRS-2 sub-scores did not further differentiate study groups, while Delis-Kaplan Executive Function System letter fluency scores favored placebo group (p<0.05). Injection site reactions and gastrointestinal symptoms were common adverse events (AEs). Eleven serious AEs (9 liraglutide, 2 placebo) were reported, none related to the trial intervention.

Interpretation: Treatment with liraglutide is safe and improves critical features of PD, including non-motor symptoms, overall mobility, activities of daily living, and quality of life. These results validate similar outcomes reported with other GLP-1 agonists and offer new strategies to comprehensively treat a larger variety of PD symptoms.

Trial Registration: Our trial is registered with ClinicalTrials.gov, NCT02953665

Funding: Cure Parkinson’s

Declaration of Interest: MT has received honoraria from Abbott, Acorda, Allergan, Boston Scientific and Medtronic. ET reports consulting fees from Abbvie. JW privately owns stocks in Novo Nordisk, the study drug manufacturer. All other authors declare no competing interests.

Ethical Approval: Cedars-Sinai Institutional Review Board (CSMC IRB) approved this study, IRB approval number, (Pro#0044598) dated 8/8/2016.

Keywords: Parkinson's disease, liraglutide, glucagon-like peptide-1, clinical trial

Suggested Citation

Hogg, Elliot and Wu, Tina and Bresee, Catherine and Wertheimer, Jeffrey and Malatt, Camille and Tan, Echo and Pomeroy, Hayley and Nuno, Miriam and Wyse, Richard and Tagliati, Michele, A Phase II, Randomized, Double-Blinded, Placebo-Controlled Trial of Liraglutide in Parkinson's Disease. Available at SSRN: https://ssrn.com/abstract=4212371 or http://dx.doi.org/10.2139/ssrn.4212371

Elliot Hogg

Cedars Sinai Medical Center - Department of Neurology ( email )

Tina Wu

Cedars Sinai Medical Center - Department of Neurology ( email )

Catherine Bresee

Cedars Sinai Medical Center - Biostatistics Core ( email )

Jeffrey Wertheimer

Cedars Sinai Medical Center - Department of Physical Medicine and Rehabilitation ( email )

Camille Malatt

Cedars Sinai Medical Center - Department of Neurology ( email )

Echo Tan

Cedars Sinai Medical Center - Department of Neurology ( email )

Hayley Pomeroy

Cedars Sinai Medical Center - Department of Neurology ( email )

Miriam Nuno

University of California, Davis - Department of Public Health Sciences ( email )

Richard Wyse

Cure Parkinson's ( email )

Michele Tagliati (Contact Author)

Cedars Sinai Medical Center - Department of Neurology ( email )

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