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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
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
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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]
The cited source says what the claim attributes to it.
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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Buse, J. B., Rosenstock, J., Sesti, G., Schmidt, W. E., Montanya, E., Brett, J. H., Zychma, M., & Blonde, L. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60659-0 · Cited by 1,503
Eng, J., Kleinman, W. A., Singh, L., Singh, G., & Raufman, J. P. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42531-8 · Cited by 1,000
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
Items 201–300 of 887
Ferrari, F., Moretti, A., & Villa, R. F. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108277 · Cited by 63
Ferreira, S. T. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12959 · Cited by 59
Lin, K.-J., Wang, T., Chen, S., Lin, K.-L., Liou, C., Lan, M., Chuang, Y., Chuang, J., Wang, P., Lee, J., et al. (2021) · Antioxidants · doi:10.3390/antiox10121935 · Cited by 63
Alpha-Synuclein Glycation and the Action of Anti-Diabetic Agents in Parkinson’s Disease
König, A., Miranda, H. V., & Outeiro, T. F. (2018) · Journal of Parkinson s Disease · doi:10.3233/jpd-171285 · Cited by 59
“Several other studies suggest that anti-diabetic drugs such as exenatide and metformin are neuroprotective in several models of PD and in patients [90, 91].”
BackgroundŠkorvánek, M., Feketeová, E., Kurtis, M. M., Rusz, J., & Šonka, K. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00376 · Cited by 58
Drug Repurposing in Parkinson’s Disease
Athauda, D. S., & Foltynie, T. (2018) · CNS Drugs · doi:10.1007/s40263-018-0548-y · Cited by 59
Self-citationA Stage-Based Approach to Therapy in Parkinson’s Disease
Carrarini, C., Russo, M., Dono, F., Pietro, M. D., Rispoli, M. G., Stefano, V. D., Ferri, L., Barbone, F., Vitale, M., Thomas, A., et al. (2019) · Biomolecules · doi:10.3390/biom9080388 · Cited by 58
“Exenatide, approved for the treatment of diabetes mellitus type 2, is another agent that has been investigated for its potential neuroprotective effects [255].”
BackgroundTranslational molecular imaging and drug development in Parkinson’s disease
Haider, A., Elghazawy, N. H., Dawoud, A., Gebhard, C., Wichmann, T., Sippl, W., Hoener, M. C., Arenas, E., & Liang, S. H. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00600-z · Cited by 60
“…double-blind and placebo-controlled trial, patients with moderate idiopathic PD received the GLP-1 receptor agonist, exenatide, once weekly for 48 weeks in addition to their regular medication, prompting a significant improvement of their clinical scores, as compared to the placebo group [185].”
BackgroundMethodExploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning
Kim, J. A., & Yoo, H. J. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0242 · Cited by 71
“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].”
Onoviran, O. F., Li, D., Smith, S. T., & Raji, M. A. (2019) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622319862691 · Cited by 64
Elbassuoni, E., & Ahmed, R. F. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104583 · Cited by 57
West, J., Li, M., Wong, S., Le, G. H., Teopiz, K. M., Valentino, K., Dri, C. E., & McIntyre, R. S. (2025) · Neurology and Therapy · doi:10.1007/s40120-025-00724-y · Cited by 63
“Exenatide improved motor scores, that were sustained past the exposure to exenatide [26].”
InfluentialJabbari, E., Woodside, J., Guo, T., Magdalinou, N. K., Chelban, V., Athauda, D. S., Lees, A. J., Foltynie, T., Houlden, H., Church, A., et al. (2019) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-320151 · Cited by 58
Self-citationInventing Liraglutide, a Glucagon-Like Peptide-1 Analogue, for the Treatment of Diabetes and Obesity
Knudsen, L. B. (2019) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.9b00048 · Cited by 59
The pleiotropic of GLP-1/GLP-1R axis in central nervous system diseases
Zhang, L., Zhang, W., & Tian, X. (2023) · International Journal of Neuroscience · doi:10.1080/00207454.2021.1924707 · Cited by 54
“0318) on part 3 of the MDS-uPDRS in an off-medication state compared with those given placebo 12 weeks after stopping exenatide [42].”
MethodBiessels, G. J., Verhagen, C., Janssen, J., van den Berg, E., Wallenstein, G., Zinman, B., Espeland, M. A., & Johansen, O. E. (2021) · Diabetologia · doi:10.1007/s00125-021-05393-8 · Cited by 61
“Incretin-based glucose-loweringmedications have emerged as a potential therapeutic agent for Alzheimer’s disease [18].”
BackgroundLee, M. M. Y., Petrie, M. C., McMurray, J. J. V., & Sattar, N. A. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.311904 · Cited by 57
Update in therapeutic strategies for Parkinson's disease
Kulisevsky, J., de Oliveira, L. M., & Fox, S. H. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000579 · Cited by 54
Sharma, N., Soni, R., Sharma, M., Chatterjee, S., Parihar, N., Mukarram, M., kale, R., Sayyed, A. A., Behera, S. K., & Khairnar, A. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03005-z · Cited by 54
“Furthermore, in a proof-of-concept research and a randomized, placebo-controlled trial, Exenatide was found to have a positive effect in mitigating motor deficits in PD patients [23, 24].”
BackgroundThe Involvement of Neuroinflammation in the Onset and Progression of Parkinson’s Disease
Jurcău, A., Andronie-Cioară, F. L., Nistor-Cseppento, C. D., Pașcalău, N., Rus, M., Vasca, E., & Jurcău, M. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914582 · Cited by 58
“GLP-1 analogue Exenatide Phase 2 NCT01971242 Positive effects on off-medication motor scores [320]”
Neuroprotection of Exendin-4 by Enhanced Autophagy in a Parkinsonian Rat Model of α-Synucleinopathy
Bu, L.-L., Liu, Y., Shen, Y., Fan, Y., Yu, W., Jiang, D., Tang, Y., Yang, Y., Wu, P., Zuo, C., et al. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01018-5 · Cited by 54
Sánchez‐Gómez, A., Díaz, Y., Duarte‐Salles, T., Compta, Y., & Martı́, M. J. (2021) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2021.06.002 · Cited by 54
Wang, R.-F., Xue, G., Hölscher, C., Tian, M.-J., Feng, P., Zheng, J.-Y., & Li, D. (2018) · Epilepsy Research · doi:10.1016/j.eplepsyres.2018.03.009 · Cited by 55
“A phase II double-blind, placebo controlled trial that recently finished confirmed the results from the pilot study, demonstrating that the strategy of activating GLP-1 receptors in the brain is a viable strategy in treating neurodegenerative disorders [50].”
BackgroundResultPeripheral insulin and amylin levels in Parkinson's disease
Sánchez-Gómez, A., Alcarraz-Vizán, G., Fernández, M., Fernández-Santiago, R., Ezquerra, M., Cámara, A., Serrano, M., Novials, A., Muñoz, E., Valldeoriola, F., et al. (2020) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2020.08.018 · Cited by 44
“Such a link might have potential pathophysiological, diagnostic and therapeutic relevance, in the current setting of great attention being paid to the potential neuroprotective effect of antidiabetic drugs [35].”
New hopes for disease modification in Parkinson's Disease
Poewe, W. H., Seppi, K., Marini, K., & Mahlknecht, P. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108085 · Cited by 53
Approaches to Disease Modification for Parkinson's Disease: Clinical Trials and Lessons Learned
Hung, A. Y., & Schwarzschild, M. A. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00964-w · Cited by 53
“The primary outcome measure, change in MDS-UPDRS motor subscale (part 3) score at 60 weeks (following 12 weeks off treatment), demonstrated modest but statistically significant improvement in motor symptoms in the treated group, though scores were actually worse in the exenatide group at 60 weeks due at least in part…”
BackgroundBiological Membrane-Penetrating Peptides: Computational Prediction and Applications
de Oliveira, E. C. L., da Costa, K. S., Taube, P. S., Lima, A. H., & Sales, C. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.838259 · Cited by 60
“Some studies displayed that the administration of this peptide peripherally can cross the BBB in humans (Hunter and Hölscher, 2012; Athauda et al., 2017), besides exhibiting neuroprotective effects on several neurodegenerative models, mainly in PD (Athauda and Foltynie, 2016).”
BackgroundRocha‐Ferreira, E., Poupon-Bejuit, L., Zelco, A., Leverin, A., Nair, S., Jonsdotter, A., Carlsson, Y., Thornton, C., Hagberg, H., & Rahim, A. A. (2018) · Brain · doi:10.1093/brain/awy220 · Cited by 51
“Exendin-4 is a drug used to treat type 2 diabetes mellitus that has also demonstrated neuroprotective properties, and is currently being tested in clinical trials for Alzheimer’s and Parkinson’s diseases.”
BackgroundResultInfluentialFine, J. M., STROEBEL, B. M., Faltesek, K. A., Terai, K., Haase, L. R., Knutzen, K. E., Kosyakovsky, J., Bowe, T. J., Fuller, A. K., Frey, W. H., et al. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134567 · Cited by 52
Therapeutic application of GLP-1 and GIP receptor agonists in Parkinson’s disease
Yang, X., Feng, P., Ji, R., Ren, Y., Wei, W., & Hölscher, C. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2079492 · Cited by 52
“This demonstrates the diseasemodifying properties of exendin-4 and the outcomes were convincing enough that Bydureon was subsequently evaluated in a similar group of PD participants for 60 weeks in a double-blind clinical trial initiated by the same investigators (NCT01971242) [76].”
BackgroundMethodResultInfluentialYu, H., Sun, T., He, X., Wang, Z., Zhao, K., An, J., Wen, L., Li, J., Li, W., & Feng, J. (2022) · Aging and Disease · doi:10.14336/ad.2022.0325 · Cited by 56
“Exenatide-treated patients had augmented tyrosine phosphorylation of IRS1 and elevated expression of downstream substrates, including total Akt and phosphorylated mTOR, in serum exosomes [162, 163].”
BackgroundEbrahimi, P., Batlle, J. C., Ayati, A., Maqsood, M. H., Long, C., Tarabanis, C., McGowan, N., Liebers, D. T., Laynor, G., Hosseini, K., et al. (2025) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2025.0091 · Cited by 51
Cherney, D. Z. I., Udell, J. A., & Drucker, D. J. (2021) · Med · doi:10.1016/j.medj.2021.10.004 · Cited by 54
Zhang, Y., Xu, S., Qian, Y., Mo, C., Ai, P., Yang, X., & Xiao, Q. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1099018 · Cited by 51
“Enhancement of GLP-1 secretion by GLP-1R agonist can exert protective effects in PD (Kim et al., 2009; Athauda et al., 2017).”
BackgroundThe liver–brain axis in metabolic dysfunction-associated steatotic liver disease
Mikkelsen, A. C. D., Kjærgaard, K., Schapira, A. H. V., Mookerjee, R. P., & Thomsen, K. L. (2024) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(24)00320-0 · Cited by 60
Animal Venom Peptides as a Treasure Trove for New Therapeutics Against Neurodegenerative Disorders
Yang, X., Wang, Y., Wu, C., & Ling, E. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666181031122438 · Cited by 49
Hölscher, C. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.955258 · Cited by 49
“In this randomized, double-blind, and placebo-controlled phase II clinical study (NCT01971242) (Athauda et al., 2017), 60”
BackgroundTherapeutic innovation in drug repurposing: Challenges and opportunities
Recino, A., Rayner, M., Rohn, J. L., Pasqua, O. E. D., Recino, A., Rayner, M. L. D., Rohn, J. L., Carter, B., Cupani, A., Dahlmann-Noor, A. H., et al. (2025) · Drug Discovery Today · doi:10.1016/j.drudis.2025.104390 · Cited by 48
Self-citationIncretin Mimetics as Rational Candidates for the Treatment of Traumatic Brain Injury
Glotfelty, E. J., Delgado, T., Tovar‐y‐Romo, L. B., Luo, Y., Hoffer, B. J., Olson, L., Karlsson, T. E., Mattson, M. P., Harvey, B. K., Tweedie, D., et al. (2019) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.9b00003 · Cited by 48
Self-citationBader, M., Li, Y., Tweedie, D., Shlobin, N. A., Bernstein, A., Rubovitch, V., Tovar‐y‐Romo, L. B., DiMarchi, R. D., Hoffer, B. J., Greig, N. H., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00356 · Cited by 48
Self-citationPathogenesis‐targeted therapeutic strategies in Parkinson's disease
Jankovic, J. J. (2018) · Movement Disorders · doi:10.1002/mds.27534 · Cited by 47
Li, Y., Glotfelty, E. J., Karlsson, T. E., Fortuno, L. V., Harvey, B. K., & Greig, N. H. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15521 · Cited by 47
“…in reversing dopaminergic cell death in animal models of PD (Chen et al., 2018; Glotfelty et al., 2020; Li et al., 2009; Salcedo et al., 2012) and recently have shown benefits in a human PD clinical trial (Athauda et al., 2017), with further ones planned or ongoing (Glotfelty et al., 2020).”
BackgroundSelf-citationUyar, M., Lezius, S., Buhmann, C., Pötter‐Nerger, M., Schulz, R. J., Meier, S., Gerloff, C. P., Kühle, J., & Choe, C. (2022) · Movement Disorders · doi:10.1002/mds.29009 · Cited by 46
“Key Words: neurofilament; Simoa; glycemia Epidemiological studies convincingly suggest a link between diabetes and Parkinson’s disease (PD).1-3 Record-linkage cohort studies, meta-analyses, and Mendelian randomization analyses found evidence for an increased risk of PD in patients with diabetes.2,4 Besides PD risk, pr…”
BackgroundInfluentialParkinson’s Disease and Sugar Intake—Reasons for and Consequences of a Still Unclear Craving
Haas, J., Berg, D., Bosy‐Westphal, A., & Schaeffer, E. (2022) · Nutrients · doi:10.3390/nu14153240 · Cited by 46
Le, T. D. V., Fathi, P. A., Watters, A. B., Ellis, B. J., Besing, G.-L. K., Bozadjieva-Kramer, N., Perez, M. B., Sullivan, A. I., Rose, J. P., Baggio, L. L., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101718 · Cited by 49
Watanabe, H., Dijkstra, J. M., & Nagatsu, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042009 · Cited by 48
von Linstow, C. U., Gan‐Or, Z., & Brundin, P. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00218-x · Cited by 45
Semaglutide seems to be more effective the other GLP-1Ras
Holst, J. J., & Madsbad, S. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2017.11.10 · Cited by 47
“However, studies in humans have not supported the use of GLP-1 RA in cerebral diseases (19), except for one clinical trial of 48 weeks, which suggested that exenatide once weekly had positive effects in Parkinson’s disease, which were sustained beyond the period of exposure (20).”
BackgroundProgress of Pharmacological Approaches in Parkinson's Disease
Zeuner, K. E., Schäffer, E., Hopfner, F., Brüggemann, N., & Berg, D. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1374 · Cited by 48
Scavone, C., di Mauro, G., Mascolo, A., Berrino, L., Rossi, F., & Capuano, A. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00111 · Cited by 44
“Once the new medicine is authorized, based on data demonstrating the positive benefit/risk profile, the realworld effectiveness and safety of the drug is assessed during phase IV studies (Auricchio et al., 2017; Mascolo et al., 2017).”
BackgroundFoltynie, T., & Athauda, D. S. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.008 · Cited by 46
Self-citationBiomarker and therapeutic potential of peripheral extracellular vesicles in Alzheimer’s disease
Vandendriessche, C., Kapogiannis, D., & Vandenbroucke, R. E. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114486 · Cited by 44
Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity
Lin, H.-T., Tsai, Y.-F., Liao, P.-L., & Wei, J. C.-C. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.21016 · Cited by 43
Zhang, L., Li, C., Zhang, Z., Zhang, Z., Jin, Q., Li, L., & Hölscher, C. (2022) · Parkinson s Disease · doi:10.1155/2022/1428817 · Cited by 45
“A pilot clinical trial in PD patients (NCT01174810) had shown good efects [39, 40], and a follow-up phase II placebo-controlled clinical trial con-frmed the protective efects in PD patients [41, 42].”
Nakmode, D. D., Day, C. M., Song, Y., & Garg, S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15051503 · Cited by 48
“In patients with moderate PD, the effects of subcutaneous exenatide were investigated in a recent double-blinded placebo-controlled experiment [88].”
Lisco, G., Tullio, A. D., Iovino, M., Disoteo, O., Guastamacchia, E., Giagulli, V. A., & Triggiani, V. (2023) · Biomedicines · doi:10.3390/biomedicines11112993 · Cited by 51
Detrimental effect of type 2 diabetes mellitus in a large case series of Parkinson's disease
Chung, S. J., Jeon, S., Yoo, H. S., Kim, G., Oh, J. S., Kim, J. S., Evans, A. C., Sohn, Y. H., & Lee, P. H. (2018) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2018.08.023 · Cited by 44
Metformin as a Potential Neuroprotective Agent in Prodromal Parkinson's Disease—Viewpoint
Sportelli, C., Urso, D., Jenner, P. G., & Chaudhuri, К. R. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00556 · Cited by 47
Li, Z., Chen, X., Vong, J. S. L., Zhao, L., Huang, J., Yan, L. Y. C., Ip, B., Wing, Y. K., Lai, H.-M., Mok, V. C. T., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02208-9 · Cited by 42
Tetorou, K., Sisa, C., Iqbal, A., Dhillon, K., & Hristova, M. (2021) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2021.709301 · Cited by 43
Alpha synuclein post translational modifications: potential targets for Parkinson’s disease therapy?
Brembati, V., Faustini, G., Longhena, F., & Bellucci, A. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1197853 · Cited by 43
“In a next randomized, placebo-controlled, double-blind trial the authors analyzed the improvements of exenatide treated PD patients regarding motor abilities (Athauda et al., 2017), mood and cognition (Athauda et al.”
BackgroundTang, H., Lu, Y., Okun, M. S., Donahoo, W. T., Ramirez‐Zamora, A., Wang, F., Huang, Y., Armstrong, M. J., Svensson, M., Virnig, B. A., et al. (2024) · Movement Disorders · doi:10.1002/mds.29992 · Cited by 44
“29 Then, a post hoc analysis indicated the potential bene fi ts of exenatide for non-motor symptoms like mood and emotional well-being, although these effects were transient.”
Is Exenatide a Treatment for Parkinson’s Disease?
Athauda, D. S., Wyse, R. K. H., Brundin, P., & Foltynie, T. (2017) · Journal of Parkinson s Disease · doi:10.3233/jpd-171192 · Cited by 42
Self-citationDrug repositioning in drug discovery of T2DM and repositioning potential of antidiabetic agents
Zhu, S., Bai, Q., Li, L., & Xu, T. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.05.057 · Cited by 42
“A meta -analysis [134] and several clinical trials [135,136] have demonstrated the therapeutic potential of exenatide in improving motor symptoms in PD patients.”
BackgroundNeuroprotective effects of GLP-1 class drugs in Parkinson’s disease
Lv, D., Feng, P., Guan, X., Liu, Z., Li, D., Xue, C., Bai, B., & Hölscher, C. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1462240 · Cited by 46
Enteroendocrine cells: the gatekeepers of microbiome-gut-brain communication
Grundeken, E., & Aidy, S. E. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00810-x · Cited by 48
“Treatedgroupsexhibitedreducedmotordisability progression 125 or evenimprovement 126,127 compared to controls.”
Mohiuddin, M. S., Himeno, T., Inoue, R., Miura‐Yura, E., Yamada, Y., Nakai‐Shimoda, H., Asano, S., Kato, M., Motegi, M., Kondo, M., et al. (2019) · Journal of Diabetes Research · doi:10.1155/2019/9426014 · Cited by 44
“Furthermore, the neuroprotective effects of Ex4 have been already proven in one clinical trial of Parkinson’s disease [35].”
Histamine-4 receptor antagonist ameliorates Parkinson-like pathology in the striatum
Fang, Q., Xicoy, H., Shen, J., Luchetti, S., Dai, D., Zhou, P., Qi, X., Martens, G. J. M., Huitinga, I., Swaab, D. F., et al. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.11.036 · Cited by 41
“It should be noted that various aspects of the top three from the list - gastric inhibitory polypeptide receptor, adrenoceptor alpha 2B and purinergic receptor P2X7 - have been tested as potential treatments for PD (Athauda et al., 2017; Savola et al., 2003) (ClinicalTrails.gov Id: NCT03918616).”
Qin, X., Zhang, X., Li, P., Wang, M., Li, Y., Bao, Z., & Liu, Q. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.678649 · Cited by 41
Self-citationDiabetes mellitus and Parkinson’s disease: dangerous liaisons between insulin and dopamine
de Iuliis, A., Montinaro, E., Fatati, G., Plebani, M., & Colosimo, C. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.320965 · Cited by 37
“…therapy in ameliorating motor symptom severity in PD patients (Athauda et al., 2014), opening an intense discussion about the development of this novel therapeutic strategy, also as a potential disease-modifying treatment (Simuni and Brundin, 2014; Athauda et al., 2017; Jankovic, 2017).”
BackgroundFrom metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics
Roy, A., Dawson, V. L., & Dawson, T. M. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00712 · Cited by 43
Li, L., Zhang, L.-Y., Jin, Q.-Q., & Hölscher, C. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.303045 · Cited by 38
Su, Y., Liu, N., Zhang, Z., Li, H., Ma, J., Yuan, Y., Shi, M., Liu, J., Zhao, Z., Zhang, Z., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175029 · Cited by 42
Jensen, M. E., Galli, A., Thomsen, M., Jensen, K. L., Thomsen, G. K., Klausen, M. K., Vilsbøll, T., Christensen, M., Holst, J. J., Owens, A. W., et al. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104772 · Cited by 42
Genotype-driven therapeutic developments in Parkinson’s disease
Prasuhn, J., & Brüggemann, N. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00281-8 · Cited by 42
Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson′s disease
Yu, H., Sun, T., Wang, Z., Li, H., Xu, D., An, J., Wen, L.-L., Li, J., Li, W., & Feng, J. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.360242 · Cited by 40
“Moreover, some clinical trials have been conducted to test the effectiveness and safety of exenatide – a synthetic exendin-4 compound – in PD treatment (Athauda et al., 2017, 2019).”
BackgroundAdvances in GLP-1 receptor agonists for pain treatment and their future potential
He, Y., Xu, B., Zhang, M., Chen, D., Wu, S., Gao, J., Liu, Y., Zhang, Z., Kuang, J., & Fang, Q. (2025) · The Journal of Headache and Pain · doi:10.1186/s10194-025-01979-4 · Cited by 43
The Gut‐Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications
Menozzi, E., Schapira, A. H. V., & Borghammer, P. (2025) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.70029 · Cited by 42
“127 Even though these results suggested a disease-modifying effect, it is possible that the observed bene fi ts were secondary to long-lasting symptomatic effects.”
Parkinson’s disease and osteoporosis: basic and clinical implications
Figueroa, C. A., & Rosen, C. J. (2020) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2020.1756772 · Cited by 40
“In addition, insulin resistance and Type 2 Diabetes Mellitus (T2DM) are more common in PD. Alternative approaches that treat these metabolic conditions may also help in improvingmotor function, as recently noted froma trial in England with exenatide, a GLP-1 agonist used to treat T2DM [98].”
BackgroundAntidiabetic Agents for Treatment of Parkinson’s Disease: A Meta-Analysis
Wang, S., Wu, S., Chen, T.-C., & Chuang, C. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17134805 · Cited by 39
“The patients with PD were followed for 12 months after cessation of the trials [22,23].”
BackgroundChou, S., Chan, L., Chung, C., Chiu, J.-Y., Hsieh, Y., & Hong, C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.564641 · Cited by 35
Wu, P., Dong, Y., Chen, J., Guan, T., Cao, B., Zhang, Y., Qi, Y., Guan, Z., & Wang, Y. (2022) · Neurotoxicity Research · doi:10.1007/s12640-021-00460-9 · Cited by 41
“GLP-1 agonists or inhibitors of GLP-1 degrading enzymes can improve the motor symptoms of patients with PD (Athauda et al. 2017; Kim et al. 2017); however, the mechanism of action remains unclear.”
BackgroundBirajdar, S. V., Mazahir, F., Alam, M. I., Kumar, A., & Yadav, A. K. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.176117 · Cited by 37
Dei, A., Micheli, M. M., Aldigeri, R., Gardini, S., Pellegrini, F. F., Perini, M., Messa, G., Antonini, M., Spigoni, V., Cinquegrani, G., et al. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-024-02320-7 · Cited by 41
“Human data demonstrated that cerebrospinal fluid levels of exenatide are 2% of plasma levels in subjects with Parkinson disease following long-acting exenatide administration [41] and higher systemic doses might be necessary to be clinically relevant on the CNS.”
BackgroundArredouani, A. (2025) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2025.108824 · Cited by 36
Insulin resistance: The role in comorbid type 2 diabetes mellitus and depression
Yao, J., Zhu, C., Sun, Y., Huang, Y., Li, Q., Liao, H.-M., Deng, X.-J., & Li, W.-M. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106218 · Cited by 45
Novel Targets for Parkinson’s Disease: Addressing Different Therapeutic Paradigms and Conundrums
Rane, P., Sarmah, D., Bhute, S., Kaur, H., Goswami, A., Kalia, K., Borah, A., Dave, K. R., Sharma, N., & Bhattacharya, P. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00180 · Cited by 35
The BRadykinesia Akinesia INcoordination (BRAIN) Tap Test: Capturing the Sequence Effect
Hasan, H., Burrows, M., Athauda, D. S., Hellman, B., James, B., Warner, T. T., Foltynie, T., Giovannoni, G., Lees, A. J., & Noyce, A. J. (2019) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12798 · Cited by 36
Self-citationCommon Variants Coregulate Expression of GBA and Modifier Genes to Delay Parkinson's Disease Onset
Schierding, W. S., Farrow, S. L., Fadason, T., Graham, O. E. E., Pitcher, T. L., Qubisi, S., Davidson, A. J., Perry, J. K., Anderson, T., Kennedy, M. A., et al. (2020) · Movement Disorders · doi:10.1002/mds.28144 · Cited by 37
Khor, S. L. Q., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2023) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527322666230330093829 · Cited by 37
The gut microbiota modulate locomotion via vagus-dependent glucagon-like peptide-1 signaling
Lai, T.-T., Tsai, Y.-H., Liou, C.-W., Fan, C., Hou, Y.-T., Yao, T.-H., Chuang, H.-L., & Wu, W. (2024) · npj Biofilms and Microbiomes · doi:10.1038/s41522-024-00477-w · Cited by 40
Wang, V., Kuo, T., Huang, E. Y., Ma, K., Chou, Y., Fu, Z.-Y., Lai, L.-W., Jung, J. H., Choi, H.-I., Choi, D., et al. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.1c00013 · Cited by 35
Self-citationThe gut–brain axis in early Parkinson’s disease: from prodrome to prevention
Oliver, P. J., Civitelli, L., & Hu, M. T. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13138-5 · Cited by 42
Zhou, L., Xu, Z., Oh, Y., Gamuyao, R., Lee, G., Xie, Y., Cho, H., Lee, S., & Duh, E. J. (2021) · JCI Insight · doi:10.1172/jci.insight.93382 · Cited by 34
“Strikingly, exenatide has exhibited beneficial effects on motor scores in a clinical trial of patients with Parkinson’s disease (19).”
BackgroundPathogenesis of Parkinson’s Disease
Xiao, B., Zhou, Z., Chao, Y., & Tan, E.-K. (2025) · Neurologic Clinics · doi:10.1016/j.ncl.2024.12.003 · Cited by 36
Bader, M., Li, Y., Lecca, D., Rubovitch, V., Tweedie, D., Glotfelty, E. J., Rachmany, L., Kim, H. K., Choi, H., Hoffer, B. J., et al. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.11.023 · Cited by 34
Self-citationNeuroprotective Effects of Brain-Gut Peptides: A Potential Therapy for Parkinson’s Disease
Dong, D., Xie, J.-X., & Wang, J. (2019) · Neuroscience Bulletin · doi:10.1007/s12264-019-00407-3 · Cited by 34
“Next, a single-center, double-blind, randomized, placebo-controlled trial, in which moderate PD patients were treated with exenatide or placebo once a week for 48 weeks, followed by a washout period of 12 weeks was carried out [31].”
MethodDelva, A., Laere, K. V., & Vandenberghe, W. (2022) · Movement Disorders · doi:10.1002/mds.29148 · Cited by 36
“6 hours) withdrawal of ropinirole, pramipexole, rasagiline, and safinamide.(26,27)”
Isop, L. M., Neculau, A. E., Necula, R. D., Kakucs, C., Moga, M., & Dima, L. (2023) · Pharmaceuticals · doi:10.3390/ph16121714 · Cited by 36
“A recent randomized, double-blind, placebo-controlled clinical trial unveiled that exenatide, an agonist of GLP-1, could potentially yield beneficial outcomes in terms of motor symptoms for individuals with PD [257].”
GLP-1 and the Degenerating Brain: Exploring Mechanistic Insights and Therapeutic Potential
Moaket, O. S., Obaid, S. E., Obaid, F. E., Shakeeb, Y. A., Elsharief, S. M., Tania, A., Darwish, R., Butler, A. E., & Moin, A. S. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110743 · Cited by 40
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
