The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
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.
In the citing paper
“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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In the citing paper
“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 the citing paper
“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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In the citing paper
“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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In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
In the citing paper
“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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Citations
Cites
1 retracted
Rampersaud, N., Harkavyi, A., Giordano, G., Lever, R., Whitton, J., & Whitton, P. S. (2012) · Neuropeptides · doi:10.1016/j.npep.2012.07.004 · Cited by 32
RetractedHughes, A. J., Daniel, S. E., Kilford, L., & Lees, A. J. (1992) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.55.3.181 · Cited by 10,378
Self-citationSystematic review of levodopa dose equivalency reporting in Parkinson's disease
Tomlinson, C. L., Stowe, R. L., Patel, S., Rick, C., Gray, R. G., & Clarke, C. E. (2010) · Movement Disorders · doi:10.1002/mds.23429 · Cited by 4,219
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Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies
Elashoff, M., Matveyenko, A. V., Gier, B., Elashoff, R., & Butler, P. C. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.018 · Cited by 944
A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease
Olanow, C. W., Rascol, O., Hauser, R. A., Feigin, P. D., Jankovic, J. J., Lang, A. E., Langston, J. W., Melamed, E., Poewe, W. H., Stocchi, F., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0809335 · Cited by 902
Microglial activation and dopamine terminal loss in early Parkinson's disease
Ouchi, Y., Yoshikawa, E., Sekine, Y., Futatsubashi, M., Kanno, T., Ogusu, T., & Torizuka, T. (2005) · Annals of Neurology · doi:10.1002/ana.20338 · Cited by 864
Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL‐PET study
Whone, A. L., Watts, R. L., Stoessl, A. J., Davis, M. R., Reske, S. N., Nahmias, C., Lang, A. E., Rascol, O., Ribeiro, M. J., Rémy, P., et al. (2003) · Annals of Neurology · doi:10.1002/ana.10609 · Cited by 831
Incretin-based therapies for type 2 diabetes mellitus
Lovshin, J. A., & Drucker, D. J. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.48 · Cited by 645
Cited by
Sorted by citations
Bloem, B. R., Okun, M. S., & Klein, C. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00218-x · Cited by 3,920
Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1
Drucker, D. J. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.001 · Cited by 2,170
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art
Nauck, M. A., Quast, D. R., Wefers, J., & Meier, J. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101102 · Cited by 1,647
“In clinical trials, exenatide improved the MDS-UPDRS score (a standardized assessment scale for patients with Parkinson’s disease) [230,231].”
BackgroundBalestrino, R., & Schapira, A. H. V. (2020) · European Journal of Neurology · doi:10.1111/ene.14108 · Cited by 1,508
“Further research is needed to clarify whether the result is due to a symptomatic or disease-modifying effect [111].”
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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