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Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial
Open accessAbstract
Background Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial.Methods In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. Eligible patients were aged 25-75 years, had idiopathic Parkinson's disease as measured by Queen Square Brain Bank criteria, were on dopaminergic treatment with wearing-off effects, and were at Hoehn and Yahr stage 2·5 or less when on treatment. Randomisation was by web-based randomisation with a two strata block design according to disease severity. Patients and investigators were masked to treatment allocation. The primary outcome was the adjusted difference in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. All efficacy analyses were based on a modified intention-to-treat principle, which included all patients who completed any post-randomisation follow-up assessments. The study is registered at ClinicalTrials.gov (NCT01971242) and is completed.Findings Between June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI -2·6 to 0·7) in the exenatide group and worsened by 2·1 points (-0·6 to 4·8) in the placebo group, an adjusted mean difference of -3·5 points (-6·7 to -0·3; p=0·0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions.Interpretation Exenatide had positive effects on practically defined off-medication motor scores in Parkinson's disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson's disease, and effects on everyday symptoms should be examined in longer-term trials.Funding Michael J Fox Foundation for Parkinson's Research.
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“Three clinical trials consistently describe a slowed decline in motor function when using the short-acting GLP-1 receptor agonists exenatide and lixisenatide in people with Parkinson's disease; 102-104”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [102]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Treatment with exenatide or lixisenatide for 1 year produced a modest but positive effect on Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III scores in people with recently diagnosed Parkinson’s disease (15, 53).”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [15]
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“This discrepancy may reflect differences in the neuroprotective mechanisms of semaglutide and tirzepatide vs earlier GLP-1RAs, such as exenatide, liraglutide, and lixisenatide, which have demonstrated favorable clinical benefits in early-stage Parkinson disease.33,50”
From Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity (2025) · cites this paper as [50]
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“In Parkinson's disease, phase II trials have shown that GLP-1 RAs such as exenatide and lixisenatide improve motor activity compared to placebo,53,54 and liraglutide has shown improvements in non-motor symptoms, mobility, and quality of life.55”
From The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions (2025) · cites this paper as [53]
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“There is increasing evidence from animal studies and clinical trials to suggest that GLP-1 receptor agonists could be beneficial in the treatment of PD, and one study using a prebiotic supplement that enhanced SCFA levels showed an increase GLP-1 levels in mouse models [141–144].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [142]
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“Multiple GLP-1 medicines, including exenatide (15), liraglutide (16), semaglutide (17, 18), and tirzepatide (19), reduce plasma CRP levels in people living with T2D and/or obesity.”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [15]
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“Moreover, GLP-1 receptors interact with various neurotransmitter systems such as serotonin, dopamine, and glutamate, which are essential for mood regulation and may contribute to the onset of depression and other psychological disorders [82].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [82]
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“There is increasing evidence from animal studies and clinical trials to suggest that GLP-1 receptor agonists could be beneficial in the treatment of PD, and one study using a prebiotic supplement that enhanced SCFA levels showed an increase GLP-1 levels in mouse models [141–144].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [142]
Experimental — accuracy not yet measuredIn the citing paper
“exenatide, administered at the dose approved for type 2 diabetes treatment, crosses the BBB in appreciable quantities and improves the motor and cognitive function of PD patients.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [616]
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“This study provides in vivo evidence that “beta-cell rest” can at least temporarily allow insulin secretory capacity recovery, and in vitro studies examining the effect of diazoxide on diabetic human islets produced similar findings.177”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [176]
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Manfready, R. A., Engen, P. A., Metman, L. V., Sanzo, G., Goetz, C. G., Hall, D. A., Forsyth, C. B., Raeisi, S., Voigt, R. M., & Keshavarzian, A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.660942 · Cited by 24
Aquino, C. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.694329 · Cited by 20
“Exenatide (47) Antihyperglycemic; glucagon-like peptide 1”
Poupon-Bejuit, L., Hughes, M. P., Liu, W., Geard, A. F., Faour-Slika, N., Whaler, S. M., Massaro, G., & Rahim, A. A. (2022) · Scientific Reports · doi:10.1038/s41598-022-17338-1 · Cited by 20
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Yu, Y.-W., Hsueh, S., Lai, J.-H., Chen, Y., Kang, S.-J., Chen, K., Hsieh, T.-H., Hoffer, B. J., Li, Y., Greig, N. H., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041153 · Cited by 19
“that some 2% of plasma levels reach the brain [16].”
BackgroundSelf-citationYu, S., Chen, S., Yang, Y.-Y., Glotfelty, E. J., Jung, Y. J., Kim, H.-K., Choi, H.-I., Choi, D., Hoffer, B. J., Greig, N. H., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00785 · Cited by 19
“Whereas the brain uptake of Exendin-4 has been reported as approximately 1– 2% of its concomitant plasma level across rodent and human studies (Athauda et al., 2017; Chen et al., 2018; Bader et al., 2019; Mullins et al., 2019), that of protein-linked GLP-1R agonists remains unknown but is likely exceedingly low (Kim e…”
BackgroundSelf-citationHelal, M. M., AbouShawareb, H., Abbas, O., Haddad, R., Zain, Y. E., Osman, A. S. A., & Hassan, A. K. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01888-1 · Cited by 22
“Another factor to consider when interpreting our results with caution is the inconsistency in the endpoints across the included studies, with follow-up periods ranging from 44 to 60 weeks [27–31].”
InfluentialMitochondrial hyperactivity as a potential therapeutic target in Parkinson’s disease
Mor, D. E., & Murphy, C. T. (2020) · Translational Medicine of Aging · doi:10.1016/j.tma.2020.07.007 · Cited by 16
“The most promising results thus far were obtained for exenatide, a glucagonlike peptide-1 receptor agonist, which improved motor symptoms in a small study of PD patients, potentially by promoting mitochondrial biogenesis [14].”
ResultAnti-diabetic drug use and reduced risk of Parkinson's disease: A community-based cohort study
Rozani, V., Bezimianski, M. G., Azuri, J., Bitan, M., & Peretz, C. (2024) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2024.107132 · Cited by 18
Type 2 diabetes management in people aged over seventy-five years: targets and treatment strategies
Koufakis, T., Grammatiki, M., & Kotsa, K. (2020) · Maturitas · doi:10.1016/j.maturitas.2020.10.005 · Cited by 18
Wyse, R. K. H., Isaacs, T., Barker, R. A., Cookson, M., Dawson, T. M., Devos, D., Dexter, D. T., Duffen, J., Federoff, H. J., Fiske, B. K., et al. (2024) · Journal of Parkinson s Disease · doi:10.3233/jpd-230363 · Cited by 19
Self-citationExploring [11C]CPPC as a CSF1R-targeted PET imaging marker for early Parkinson’s disease severity
Mills, K. A., Du, Y., Coughlin, J. M., Foss, C. A., Horti, A. G., Jenkins, K. R., Skorobogatova, Y., Spiro, E., Motley, C., Dannals, R. F., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186591 · Cited by 17
Exenatide – a drug for diabetes and Parkinson disease?
Jankovic, J. J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.140 · Cited by 17
Brain Imaging of the GLP-1 Receptor in Obesity Using 68Ga-NODAGA-Exendin-4 PET
Deden, L. N., Booij, J., Grandjean, J., Homberg, J. R., Hazebroek, E. J., Gotthardt, M., & Boss, M. (2021) · Brain Sciences · doi:10.3390/brainsci11121647 · Cited by 18
“Also, in a placebo-controlled clinical study in PD, in which half of the PD patients were treated for almost 1 year with the GLP-1 analogue exenatide [27], exenatide was detectable in the cerebrospinal fluid (CSF).”
BackgroundChai, S., Liu, F., Yu, S., Yang, Z., & Sun, F. (2023) · Journal of Diabetes Investigation · doi:10.1111/jdi.14015 · Cited by 17
Beyond insulin: The Intriguing role of GLP-1 in Parkinson's disease
Verma, A., & Goyal, A. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176936 · Cited by 17
Therapeutic innovation in Parkinson’s disease: a 2020 update on disease-modifying approaches
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Girges, C., Vijiaratnam, N., Athauda, D. S., Auld, G., Gandhi, S., & Foltynie, T. (2021) · Drugs & Aging · doi:10.1007/s40266-021-00853-7 · Cited by 18
Self-citationReed, J., Bain, S. C., & Kanamarlapudi, V. (2024) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s415934 · Cited by 21
“…demonstrated anti-inflammatory actions, such as reduction of secretion of pro-inflammatory cytokines or increase in the secretion of anti-inflammatory cytokines, of GLP-1R agonists, 259 which may have future therapeutic applications for both T1D and T2D, as well as inflammatory/autoimmune diseases.”
Majumdar, M., & Badwaik, H. R. (2024) · Current Drug Targets · doi:10.2174/0113894501312703240826070530 · Cited by 16
Parkinson Disease and the Gut: A Primer for Gastroenterologists
Sharma, A., Voigt, R. M., Goetz, C. G., & Keshavarzian, A. (2025) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000003508 · Cited by 17
Chiu, W. T., Chan, L., Wu, D., Ko, T.-H., Chen, D. Y. T., & Hong, C. (2018) · European Neurology · doi:10.1159/000499378 · Cited by 16
Colca, J. R., & Finck, B. N. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.929328 · Cited by 16
“This has led to some small clinical trials using incretin agonist antidiabetic agents that have shown positive results (Athauda et al., 2017) suggesting the treatment of the underlying hyperglycemia could be useful.”
BackgroundKoponen, M., Paakinaho, A., Lin, J., Hartikainen, S. A., & Tolppanen, A. (2022) · Clinical Epidemiology · doi:10.2147/clep.s381289 · Cited by 16
“31 In addition, lower serum uric acid levels have been associated with freezing of gait, 32 and nonmotor symptoms (dysphagia, anxiety, depression, apathy), cognitive dysfunction and whole-brain gray matter volume 33 in cross-sectional studies of persons with PD.”
BackgroundInfluentialO'Brien, J. T., Chouliaras, L., Sultana, J., Taylor, J., Ballard, C. G., on behalf of the RENEWAL Study Group, Aarsland, D., Blanc, F., Boeve, B. F., Brooks, D. J., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01103-7 · Cited by 17
“It showed that bosutinib was safe and well tolerated, penetrated the BBB to inhibit Abelson kinase and reduce CSF α-synuclein and dopamine catabolism.”
BackgroundInfluentialLenka, A., & Jankovic, J. J. (2023) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2023.2177535 · Cited by 16
Chandrashekar, A., Beig, A., Wang, Y., & Schwendeman, S. P. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123213 · Cited by 16
Prospects of antidiabetic drugs in the treatment of neurodegenerative disease
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Huang, Y., Wang, X., Li, W., Yue, F., Wang, M., & Zhou, F. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s479670 · Cited by 16
Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
Sian‐Hülsmann, J., Riederer, P. F., & Michel, T. M. (2024) · Biomedicines · doi:10.3390/biomedicines12122841 · Cited by 17
“In addition to that, Athauda et al. [139,140] found higher IRS1 phosphorylation and Akt and mTOR expression in the individuals who received Exenatide, which was associated with better motor scores.”
Estato, V., Obadia, N., Chateaubriand, P. H., Figueiredo, V., Curty, M., Silva, M. C., Ferreira, R. G. L., Santa-Ritta, J., Baroni, M. C., Aragão, A., et al. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01528-0 · Cited by 19
“In clinical trials testing exenatide in nonobese and nondiabetic Parkinson’s disease patients, no noticeable effects on body weight or blood glucose were detected [23].”
Animal venoms: therapeutic tools for tackling Parkinson’s disease
Amaral, H. D. O., Monge‐Fuentes, V., Mayer, A. B., Campos, G. A. A., Lopes, K. S., Camargo, L. C., Schwartz, M. F., Galante, P., & Mortari, M. R. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.09.004 · Cited by 17
Shang, P., Baker, M. R., Banks, S. A., Hong, S., & Choi, D. (2021) · Journal of Movement Disorders · doi:10.14802/jmd.21035 · Cited by 16
Niacin for Parkinson's disease
Seamon, M., Purohit, S. B., Giri, B., Baban, B., Morgan, J. C., Chong, R. K. Y., & Wakade, C. G. (2019) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12553 · Cited by 16
Poupon-Bejuit, L., Rocha‐Ferreira, E., Thornton, C., Hagberg, H., & Rahim, A. A. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00112 · Cited by 17
“Over the past decade, a growing number of pre-clinical and now clinical studies have provided evidence of drugs licensed for the treatment of diabetes as having protective effects on the brain (Athauda et al., 2017; Rotermund et al., 2018; Mousa and Ayoub, 2019).”
BackgroundDiabetes and Parkinson disease
Das, R. R., & Unger, M. M. (2018) · Neurology · doi:10.1212/wnl.0000000000005470 · Cited by 16
“Is glycemic control then a therapeutic target to prevent PD in diabetics? If so, which hypoglycemic agents will ameliorate PD symptoms? Some distance has already been covered: a recent randomized, double-blind clinical trial demonstrated that exenatide, a glucagon-1 receptor peptide agonist used in the adjunctive trea…”
BackgroundNtetsika, T., Catrina, S., & Markaki, I. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01910 · Cited by 16
“Early phase trials on Exenatide have been performed in the UK with positive results on motor symptom progression in PD (Aviles-Olmos et al., 2013; Aviles-Olmos et al., 2014; Athauda et al., 2017) and several others are ongoing including a phase 3 trial in the UK ( Table 1 ).”
Disease-Modifying Therapies in Parkinson’s Disease
Fabbri, M., Corvol, J., & Rascol, O. (2025) · Neurologic Clinics · doi:10.1016/j.ncl.2024.12.009 · Cited by 17
Hajare, S., & Kulkarni, Y. A. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149975 · Cited by 18
Zhang, Z., Shi, M., Li, Z., Ling, Y., Zhai, L., Yuan, Y., Ma, H., Li, H., Li, Z., Zhang, Z., et al. (2023) · Parkinson s Disease · doi:10.1155/2023/7427136 · Cited by 16
“Exendin-4 can cross the BBB well and showed good efects in animal models of PD [27, 60] and in the clinic [14, 61].”
BackgroundInfluentialPharmacological interventions in human aging
Petr, M. A., Matiyevskaya, F., Osborne, B., Berglind, M., Reves, S., Zhang, B., Ezra, M. B., Carmona-Marin, L. M., Syadzha, M. F., Mediavilla, M. C., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102213 · Cited by 20
Research progress on intranasal treatment for Parkinson's disease
Wen, P., & Ren, C. (2024) · Neuroprotection/Neuroprotection (Chichester, England. Print) · doi:10.1002/nep3.42 · Cited by 18
“133 GLP ‐ 1 agonists that promote INI have been effective in PD, 134 suggesting that INI signaling may be an important therapeutic target.”
The pathogenesis of Parkinson’s disease and crosstalk with other diseases
Liu, T., GUO, D., & Wei, J. (2024) · Biocell · doi:10.32604/biocell.2024.051518 · Cited by 15
Clinical Trial Highlights: Anti-Inflammatory and Immunomodulatory Agents
Patel, B., Greenland, J. C., & Williams‐Gray, C. H. (2024) · Journal of Parkinson s Disease · doi:10.3233/jpd-240353 · Cited by 20
“61 A phase III trial of exenatide for 96 weeks in 200 participants (Exenatide-PD3) is now in its final stages.”
BackgroundMessak, M., Abdelmageed, A., Senbel, A. A., Khattab, Y. A., Mandour, Y., Shaker, O., Rehan, A. H., Oransa, S., Nasr, M., Shabeeb, A. E., et al. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-03932-3 · Cited by 16
“…on moderate PD patients by subcutaneous injection once weekly for 48 weeks, its findings showed improvement in the exenatide group over the placebo group in the motor function assessed by MDS-UPDRS III at OFF-medication state with adjusted mean difference of − 3.5 points (Athauda et al. 2017).”
InfluentialDarsalia, V., Larsson, M., Klein, T., & Patrone, C. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0674-3 · Cited by 15
“Importantly, a recent study published on Lancet this year and involving 62 patients with Parkinson’s disease (32 treated with exenatide and 30 controls) showed positive effects of exenatide on functional motor scores parameters, which were sustained beyond the period of exposure [17].”
BackgroundProtective Effects of Incretin Against Age-Related Diseases
Zhang, D., Ma, M., & Liu, Y. (2019) · Current Drug Delivery · doi:10.2174/1567201816666191010145029 · Cited by 15
Victorino, D. B., Nejm, M. B., Guimarães‐Marques, M., Scorza, F. A., & Scorza, C. A. (2021) · Pharmaceutical Medicine · doi:10.1007/s40290-020-00374-5 · Cited by 15
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Sabbagh, M. N., Cummings, J. L., Ballard, C. G., van der Flier, W. M., Heneka, M. T., Holst, J. J., Knudsen, L. B., Salloway, S., Tansey, M. G., & Drucker, D. J. (2025) · Nature Aging · doi:10.1038/s43587-025-01029-3 · Cited by 15
“Thus, GLP-1RAs are unlikely to emerge as a treatment for ALS.”
Gudenschwager, C., Chavez, I., Cárdenas, C., & González-Billault, C. E. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5586052 · Cited by 12
“Similarly, GLP1-R agonists have been used to treat diabetes and insulin resistance and based on findings in animal models, their potential to prevent or improve NDDsares being tested [109, 117].”
BackgroundGLP1-GIP receptor co-agonists: a promising evolution in the treatment of type 2 diabetes
Ciardullo, S., Morieri, M. L., DANIELE, G., Fiorentino, T. V., Mezza, T., Tricò, D., Consoli, A., Prato, S. D., Giorgino, F., Piro, S., et al. (2024) · Acta Diabetologica · doi:10.1007/s00592-024-02300-6 · Cited by 15
“Similarly, patients with Parkinson’s disease showed an improvement in motor parameters according to the criteria of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) after treatment with exenatide [25, 26].”
MethodRate of motor progression in Parkinson’s disease: a systematic review and meta-analysis
Pauwels, A., Phan, A. L. G., Ding, C., Phan, T. G., & Kempster, P. A. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1452741 · Cited by 14
Novel approaches to counter protein aggregation pathology in Parkinson's disease
Stott, S., Wyse, R. K. H., & Brundin, P. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.007 · Cited by 16
Status and future directions of clinical trials in Parkinson's disease
Söderbom, G. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.02.009 · Cited by 14
Age-related change of GLP-1R expression in rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4
Wang, L., Liu, Y., Xu, Y., Sheng, J., Pan, D., Wang, X., Yan, J., Yang, R., & Yang, M. (2018) · Brain Research · doi:10.1016/j.brainres.2018.08.022 · Cited by 14
Quiñones, M., Fernø, J., Diéguez, C., Nogueiras, R., & Al–Massadi, O. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1583642 · Cited by 14
Fraternine, a Novel Wasp Peptide, Protects against Motor Impairments in 6-OHDA Model of Parkinsonism
Mayer, A. B., de Oliveira, D. G. R., Amaral, H. D. O., Campos, G. A. A., Gonçalves, J. C., de Souza, A. C. B., Lima, M. R., Silva, L. P., & Mortari, M. R. (2020) · Toxins · doi:10.3390/toxins12090550 · Cited by 14
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NFκB1: a common biomarker linking Alzheimer's and Parkinson's disease pathology
Cunningham, A., Barrett, E., Risch, S., Lee, P. H. U., Lee, C. M., Moghekar, A., Patra, P., & Shim, J. W. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1589857 · Cited by 14
Gandhi, A., & Parhizgar, A. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1708565 · Cited by 15
“That said, for patients with T2DM or obesity who are also at high risk for neurodegeneration, choosing a GLP-1RA might offer the potential for ancillary neuroprotection, though we must await de fi nitive phase 3 outcomes before making such claims (4 – 6, 22, 23).”
Dahiya, S., Tisch, S. H., & Greenfield, J. R. (2022) · Clinical Parkinsonism & Related Disorders · doi:10.1016/j.prdoa.2022.100133 · Cited by 13
Parkinson’s Disease and Diabetes Mellitus: Synergistic Effects on Pathophysiology and GI Motility
Yan, Y., Shimoga, D., & Sharma, A. (2023) · Current Gastroenterology Reports · doi:10.1007/s11894-023-00868-7 · Cited by 13
Meta‐analysis of Association between Newer Glucose‐Lowering Drugs and Risk of Parkinson's Disease
Tang, H., Lu, Y., Okun, M. S., Donahoo, W. T., Ramirez‐Zamora, A., Wang, F., Huang, Y., Chen, W., Virnig, B. A., Bian, J., et al. (2023) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.13893 · Cited by 14
Mi, N., Ma, L., Li, X., Fu, J., Bu, X., Liu, F., Yang, F., Zhang, Y., & Yao, L. (2023) · Open Medicine · doi:10.1515/med-2023-0849 · Cited by 13
“Glp-1 provides clinical advantages in the treatment of moderate PD [38,39].”
BackgroundEmbedding Patient Input in Outcome Measures for Long‐Term Disease‐Modifying Parkinson Disease Trials
Gonzalez‐Robles, C., Bartlett, M., Burnell, M., Clarke, C. S., Haar, S., Hu, M. T., Huxford, B., Jha, A., Lawton, M., Noyce, A. J., et al. (2023) · Movement Disorders · doi:10.1002/mds.29691 · Cited by 13
“7 Although Parts II and III have been reported to have limitations in early PD, 30 both Parts I and II have been shown to be sensitive to disease progression over the fi rst decade of the PD, 31 and their sum score has been shown to be a valid 21 and applicable endpoint.”
InfluentialSelf-citationThe Contribution of Type 2 Diabetes to Parkinson’s Disease Aetiology
Ribarič, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084358 · Cited by 15
“These results were confirmed with a follow-up randomised, double-anonymized placebo control study on patients with moderate PD [143,407].”
BackgroundResultPradeloux, S., Coulombe, K., Ouamba, A. J. K., Isenbrandt, A., Calon, F., Roy, D., & Soulet, D. (2024) · Nutrients · doi:10.3390/nu16193309 · Cited by 13
Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson’s Disease
Jeong, S. H., & Lee, P. H. (2025) · Journal of Movement Disorders · doi:10.14802/jmd.25008 · Cited by 13
“27 Similarly, the potential of another GLP-1 receptor agonist, lixisenatide, in the treatment of PD has attracted considerable attention due to promising findings.”
Gamborg, M., Grand, M. K., Arvedsen, J., Meaidi, A., & Mørch, L. S. (2025) · European Journal of Neurology · doi:10.1111/ene.70075 · Cited by 13
“Exenatide has demonstrated sustained motor benefits and potential disease-modifying effects in two trials [6, 7], while liraglutide [8] has also shown improvements in daily living and motor disability.”
Au, H. C. T., Lam, P. H., Lim, P. K., & McIntyre, R. S. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106159 · Cited by 14
“…groups were observed in the Montgomery-Asberg Depression Rating Scale, Unified Dyskinesia Rating Scale, NonMotor Symptoms Severity Scale, Parkinson ’ s Disease Questionnaire summary index, or EuroQol Five Dimensions Questionnaire in both studies (Athauda et al., 2017; Aviles-Olmos et al., 2013).”
InfluentialZhang, X., Fan, Y., Luo, Y., Jin, L., & Li, S. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.46456 · Cited by 13
“While PD medications (such as levodopa) induce hyperglycemia and hyperinsulinemia [14], anti-diabetic drugs (such as metformin [15], glitazones [16], and exenatide [17]) could elicit neuroprotection in PD and might lower the risk of acquired PD in populations with diabetes.”
BackgroundRecent Advances in Drug Repurposing for Parkinson’s Disease
Chen, X., Gumina, G., & Virga, K. G. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180719144850 · Cited by 13
Lowering the risk of Parkinson’s disease with GLP-1 agonists and DPP4 inhibitors in type 2 diabetes
Bayram, E., & Litvan, I. (2020) · Brain · doi:10.1093/brain/awaa287 · Cited by 13
Lu, C., Xu, C., & Yang, J. (2024) · Medicina · doi:10.3390/medicina61010017 · Cited by 14
Llach, C.-D., Badulescu, S., Tabassum, A., Shah, H., Gill, H., Le, G. H., Vieta, E., McIntyre, R. S., Rosenblat, J. D., & Mansur, R. B. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03261-0 · Cited by 15
“A second meta-analysis [21], which included fi ve RCTs [119, 120, 128 – 130] and one prospective cohort study [131] supported these fi ndings (SMD = − 0.12, 95% CI [ − 0.21, − 0.03], p 0.01).”
InfluentialSchrag, A. E., Carroll, C., Duncan, G. W., Molloy, S., Grover, L. E., Hunter, R. M., Brown, R. G., Freemantle, N., Whipps, J., Serfaty, M. A., et al. (2022) · BMC Neurology · doi:10.1186/s12883-022-02988-5 · Cited by 12
“…size, the study will have 90% power (1-beta) to find a mean difference of change of 3 points on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor subscale (part 3), with a nominal alpha of 0.025 for each active comparison, taking the effective SD from [22].”
MethodInfluentialPharmacotherapy for Disease Modification in Early Parkinson’s Disease: How Early Should We Be?
Mahlknecht, P., & Poewe, W. (2024) · Journal of Parkinson's Disease · doi:10.3233/jpd-230354 · Cited by 13
Zhang, K., Yang, Z., Yang, Z., Du, L., Zhou, Y., Fu, S., Wang, X., Liu, D., & He, X. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176903 · Cited by 13
Kaye, A. D., Sala, K. R., Abbott, B. M., Dicke, A., Johnson, L. D., Wilson, P. A., Amarasinghe, S. N., Singh, N., Ahmadzadeh, S., Kaye, A. M., et al. (2024) · Cureus · doi:10.7759/cureus.67232 · Cited by 12
“One study looked at the neuroprotective effects of exenatide on Parkinson’s disease [28].”
BackgroundApplication of longitudinal item response theory models to modeling Parkinson’s disease progression
Zou, H., Aggarwal, V., Stebbins, G. T., Müller, M. L. T. M., Cedarbaum, J. M., Pedata, A., Stephenson, D. T., Simuni, T., & Luo, S. (2022) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12853 · Cited by 12
Khan, M. A., Haider, N., Singh, T., Bandopadhyay, R., Ghoneim, M. M., Alshehri, S., Taha, M., Ahmad, J., & Mishra, A. (2023) · Metabolic Brain Disease · doi:10.1007/s11011-023-01180-z · Cited by 12
“On the other hand, Exenatide isn't apparent if it affects the underpinning sickness process or only creates long-term clinical manifestations (Athauda et al. 2017).”
BackgroundLin, H., Lin, H., Tseng, Y.-F., Chao, J. C.-J., & Hsu, C. (2018) · Annals of Medicine · doi:10.1080/07853890.2018.1488083 · Cited by 12
“Furthermore, recent research has indicated that the glucagon-like peptide-1 (GLP1) agonist, another category of DM medication, also reduces PD risk in patients with DM [23].”
BackgroundReynolds, R. H., Botía, J. A., Nalls, M. A., (SGPD), S. G. O. P. D., Hardy, J., Taliun, S. A. G., & Ryten, M. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/442152 · Cited by 12
Obesity drugs have another superpower: taming inflammation
Lenharo, M. (2024) · Nature · doi:10.1038/d41586-024-00118-4 · Cited by 12
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Zhang, Y., Wang, C., Wang, Y., & Wang, T. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13301-y · Cited by 11
Luo, Y., Xia, Y., Gong, X., Hao, M., Wei, Q., & Liao, L. (2026) · BMC Ophthalmology · doi:10.1186/s12886-025-04559-x · Cited by 15
“The neuroprotective potential of GLP-1 has been established in models of neurodegenerative disorders, including Parkinson’s disease and Alzheimer’s disease (AD), with evidence suggesting it can modify disease progression and ameliorate pathology [29–32].”
Fujita, T., Babazono, A., Kim, S. A., Jamal, A., & Li, Y. (2021) · BMC Geriatrics · doi:10.1186/s12877-021-02685-x · Cited by 11
“Further, administering exenatide, a drug for diabetes mellitus, has been shown to have a positive effect on PD patients [26], but no participants in this study were prescribed this drug during the study period.”
BackgroundSelf-citationLiu, C., Liu, W.-H., Yang, W., Chen, L., Xue, Y., & Chen, X. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.109946 · Cited by 11
“Additionally, GLP-1R agonists may slow down the progression of established Alzheimer ’ s disease and Parkinson ’ s disease in non-diabetic patients (Gejl et al., 2016; Athauda et al., 2017).”
Bashir, B., Vishwas, S., Gupta, G., Paudel, K. R., Dureja, H., Kumar, P., Cho, H., Sugandhi, V. V., Kumbhar, P., Disouza, J., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102693 · Cited by 11
The regulation of microglia by aging and autophagy in multiple sclerosis
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Astrocytes, a Promising Opportunity to Control the Progress of Parkinson’s Disease
Sánchez, A., Moráles, I., Rodriguez‐Sabate, C., Solé-Sabater, M., & Rodrı́guez, M. (2021) · Biomedicines · doi:10.3390/biomedicines9101341 · Cited by 12
“The NLY01 and exendin-4 GLP1R agonists have proved useful for reducing DA-cell vulnerability in animal models of PD [73] and may also protect DA-cells in PD [74].”
BackgroundEl‐Shorbagi, A., Chaudhary, S., Alshemali Khadeja, A., Alabdulrazzaq Razan, F., & Alqahtani Fatma, Y. (2020) · Journal of Applied Pharmaceutical Science · doi:10.7324/japs.2020.1010015 · Cited by 11
Glycolytic metabolism supports microglia training during age-related neurodegeneration
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Xie, Y., Wang, J., Jiang, J., Liu, F., & Zhang, Y. (2023) · Neurological Sciences · doi:10.1007/s10072-023-06965-9 · Cited by 11
“There have been clinical trials experimenting with the use of GLP1a on PD patients suggesting improvement in motor and cognitive function [41, 42].”
BackgroundTranslational approaches to restoring mitochondrial function in Parkinson's disease
Mortiboys, H., Macdonald, R., Payne, T., Sassani, M., Jenkins, T. M., & Bandmann, O. (2017) · FEBS Letters · doi:10.1002/1873-3468.12920 · Cited by 11
New therapeutic developments for Parkinson disease
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Chen, Y., Shen, J., Qi, G.-X., Zha, Q., Zhang, C., Yao, W., Gao, X., & Chen, S. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108335 · Cited by 11
Exenatide Once Weekly for Management of Type 2 Diabetes: A Review
Inaishi, J., & Saisho, Y. (2022) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s288846 · Cited by 11
“Furthermore, exenatide QW as well as BID was reported to exhibit positive effects on motor scores in patients with Parkinson’s disease compared to the placebo.(57,58) Although it is unclear how to improve motor symptoms for patients with Parkinson’s disease, exenatide is expected to have neuroprotective effects in thi…”
Background
Metadata
- Authors
- Athauda, D., Maclagan, K., Skene, S. S., Bajwa-Joseph, M., Letchford, D., Chowdhury, K., Hibbert, S., Budnik, N., Zampedri, L., Dickson, J., Li, Y., Aviles-Olmos, I., Warner, T. T., Limousin, P., Lees, A. J., Greig, N. H., Tebbs, S., & Foltynie, T.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- University College London (GB)
- National Institute on Aging (US)
- Corresponding author
- Foltynie, Thomas
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 390
- Issue
- 10103
- Pages
- 1664-1675
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC5831666
- OpenAlex
- W2744843428
- Cited by
- 889
- References
- 38
- Citations by year
- 2026: 114 · 2025: 136 · 2024: 114 · 2023: 73 · 2022: 85 · 2021: 93 · 2020: 98 · 2019: 77 · 2018: 77 · 2017: 20
- FWCI
- 51.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Open Research (University of Surrey) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- National Institutes of Health (Z99 AG999999)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, exenatide, GLP-1 receptor agonists, neuroprotection, motor symptoms, off-medication state, dopaminergic therapy, neurodegeneration, adverse events, injection site reactions, gastrointestinal symptoms, drug repurposing, disease-modifying therapy
- MeSH terms
- Exenatide, Adult, Aged, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Neurologic Examination, Parkinson Disease, Peptides, Venoms, Treatment Outcome
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