• Wassilios G Meissner, Philippe Remy, Caroline Giordana, David Maltête, Pascal Derkinderen, Jean-Luc Houéto, Mathieu Anheim, Isabelle Benatru, Thomas Boraud, Christine Brefel-Courbon, Nicolas Carrière, Hélène Catala, Olivier Colin, Jean-Christophe Corvol, Philippe Damier, Estelle Dellapina, David Devos, Sophie Drapier, Margherita Fabbri, Vanessa Ferrier, Alexandra Foubert-Samier, Solène Frismand-Kryloff, Aurore Georget, Christine Germain, Stéphane Grimaldi, Clémence Hardy, Lucie Hopes, Pierre Krystkowiak, Brice Laurens, Romain Lefaucheur, Louise-Laure Mariani, Ana Marques, Claire Marse, Fabienne Ory-Magne, Vincent Rigalleau, Hayet Salhi, Amandine Saubion, Simon R W Stott, Claire Thalamas, Claire Thiriez, Mélissa Tir, Richard K Wyse, Antoine Benard, Olivier Rascol, and LIXIPARK Study Group.
• From the French Clinical Research Network (F-CRIN) for Parkinson's Disease and Movement Disorders (NS-Park-F-CRIN) (W.G.M., P.R., C. Giordana, D.M., P. Derkinderen, J.-L.H., M.A., I.B., T.B., C.B.-C., N.C., O.C., J.-C.C., P. Damier, E.D., D.D., S.D., M.F., V.F., A.F.-S., S.F.-K., S.G., C.H., L.H., P.K., B.L., R.L., L.-L.M., A.M., C.M., F.O.-M., H.S., C. Thiriez, M.T., O.R.), Centre d'Investigation Clinique (CIC) 1436 and the Departments of Clinical Pharmacology and Neurosciences, Centre Expert Parkinson, University Hospital of Toulouse, INSERM, University of Toulouse 3 (C.B.-C., H.C., M.F., F.O.-M., C. Thalamas, O.R.), and CIC 1436, INSERM (E.D., A.S.), Toulouse, Service de Neurologie des Maladies Neurodégénératives, Centre Expert Parkinson, Institut des Maladies Neurodégénératives (IMN) Clinique (W.G.M., T.B., A.F.-S., B.L.), and Service d'Information Médicale, Unité de Soutien Méthodologique à la Recherche (USMR) (A.G., C. Germain, A.B.), Centre Hospitalier Universitaire (CHU) Bordeaux, Unité Mixte de Recherche (UMR) 5293, Université de Bordeaux, Centre National de la Recherche Scientifique (CNRS), IMN, Unité Mixte de Recherche (UMR) 5293 (W.G.M., T.B., A.F.-S.), and the European Clinical Trials Platform and Development-F-CRIN, CIC-Clinical Epidemiology Unit 1401, University of Bordeaux, INSERM, Institut Bergonié, CHU Bordeaux (A.G., C. Germain, A.B.), Bordeaux, the Department of Neurology, Centre Expert Parkinson, Equipe 01-Neuropsychologie Interventionnelle L'Institut Mondor de Recherches Biomédicales, CHU Henri Mondor, INSERM et Faculté de Santé, Université Paris-Est Créteil, Créteil (P.R., H.S.), the Department of Neurology, Centre Expert Parkinson, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice (C. Giordana, V.F., C.M.), the Department of Neurology, Centre Expert Parkinson, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, UMR 1239, Rouen University Hospital, University of Rouen, INSERM, Mont-Saint-Aignan (D.M.), and the Department of Neurology, Centre Expert Parkinson, Rouen University Hospital and University of Rouen (C.H., R.L.), Rouen, the Department of Neurology, Centre Expert Parkinson, CIC 1413, CHU Nantes, INSERM, Nantes (P. Derkinderen, P. Damier), Service de Neurologie, Centre Expert Parkinson, CIC 1402, CHU Limoges, CHU Poitiers INSERM, Limoges (J.-L.H., I.B., O.C.), the Department of Neurology, Centre Expert Parkinson, Strasbourg University Hospital, and Strasbourg Federation of Translational Medicine, Strasbourg University, Strasbourg (M.A.), the Institute of Genetics and Cellular and Molecular Biology, INSERM Unité 964, CNRS-UMR 7104, University of Strasbourg, Illkirch-Graffenstaden (M.A.), the Department of Medical Pharmacology INSERM Unité 1172, Lille Neurosciences and Cognition, Centre Hospitalier Régional Universitaire, University of Lille, Lille (N.C., D.D.), the Department of Neurology, CIC Neurosciences, Sorbonne Université, Paris Brain Institute, Assistance Publique-Hôpitaux de Paris, INSERM, CNRS, Pitié-Salpêtrière Hospital, Paris (J.-C.C., L.-L.M.), the Department of Neurology, Centre Expert Parkinson, CIC 1414, CHU Pontchaillou de Rennes, INSERM, Rennes (S.D.), the Department of Neurology, Centre Expert Parkinson, CHU de Nancy, Hôpital Central, Nancy (S.F.-K., L.H.), the Department of Neurology, Centre Expert Parkinson, University Hospital La Timone, Marseille (S.G.), the Department of Neurology, Centre Expert Parkinson, University Hospital of Amiens, Amiens (P.K., M.T.), the Department of Neurology, CHU Clermont-Ferrand, Université Clermont-Auvergne, CNRS, Image Guided Clinical Neuroscience and Connectomics, Institut Pascal, Clermont-Ferrand (A.M.), the Department of Nutrition-Diabetology, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac (V.R.), and the Department of Neurology, Centre Expert Parkinson, CHU de Caen, Caen (C. Thiriez) - all in France; the Department of Medicine, University of Otago, Christchurch, and the New Zealand Brain Research Institute - both in Christchurch, New Zealand (W.G.M.); Specialized Rehabilitation Hospital, Capital Health, Abu Dhabi, United Arab Emirates (P.K.); and Cure Parkinson's, London (S.R.W.S., R.K.W.).
• N. Engl. J. Med. 2024 Apr 4; 390 (13): 117611851176-1185.

BackgroundLixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease.MethodsIn this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period. The primary end point was the change from baseline in scores on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (range, 0 to 132, with higher scores indicating greater motor disability), which was assessed in patients in the on-medication state at 12 months. Secondary end points included other MDS-UPDRS subscores at 6, 12, and 14 months and doses of levodopa equivalent.ResultsA total of 156 persons were enrolled, with 78 assigned to each group. MDS-UPDRS part III scores at baseline were approximately 15 in both groups. At 12 months, scores on the MDS-UPDRS part III had changed by -0.04 points (indicating improvement) in the lixisenatide group and 3.04 points (indicating worsening disability) in the placebo group (difference, 3.08; 95% confidence interval, 0.86 to 5.30; P = 0.007). At 14 months, after a 2-month washout period, the mean MDS-UPDRS motor scores in the off-medication state were 17.7 (95% CI, 15.7 to 19.7) with lixisenatide and 20.6 (95% CI, 18.5 to 22.8) with placebo. Other results relative to the secondary end points did not differ substantially between the groups. Nausea occurred in 46% of participants receiving lixisenatide, and vomiting occurred in 13%.ConclusionsIn participants with early Parkinson's disease, lixisenatide therapy resulted in less progression of motor disability than placebo at 12 months in a phase 2 trial but was associated with gastrointestinal side effects. Longer and larger trials are needed to determine the effects and safety of lixisenatide in persons with Parkinson's disease. (Funded by the French Ministry of Health and others; LIXIPARK ClinicalTrials.gov number, NCT03439943.).Copyright © 2024 Massachusetts Medical Society.

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