{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:08:45Z","timestamp":1780506525654,"version":"3.54.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are progressive neurodegenerative disorders characterized by alpha-synuclein pathology. As current therapies largely target symptoms, there is a clear need for disease-modifying treatments. Emerging evidence links these disorders to glucose metabolism dysregulation, suggesting antidiabetic agents may hold therapeutic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a prospective, randomized, double-blind pilot study involving 12 subjects with PD or DLB to evaluate the tolerability and preliminary effects of a dipeptidyl peptidase 4 (DPP4) inhibitor (sitagliptin 100 mg) vs. sodium glucose like transporter 2 (SGLT2) inhibitor (dapagliflozin 10 mg) over a 4-week period, compared to a placebo. We assessed changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, cognitive function, and autonomic biomarkers. Both sitagliptin and dapagliflozin were well-tolerated, with no adverse events. While no significant changes were observed in cognitive scores, a significant difference was found in the change from baseline for MDS-UPDRS part 1 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.008), part 2 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.020), and total scores (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.047) when comparing the three groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The dapagliflozin group showed more favorable trends in MDS-UPDRS scores. Limitations include small study size and duration as well as all participants had PD except one subject in the DPP4 inhibitor group with DLB. This pilot study suggests that these inhibitors are safe in PD and DLB patients. The preliminary findings, particularly the trends in the dapagliflozin group, provide a basis for larger-scale, long-term studies to confirm these potential symptomatic benefits and explore disease-modifying effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT06263673<\/jats:ext-link>\n                      , identifier: NCT06263673.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1825229","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:15:21Z","timestamp":1780067721000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-diabetic medications to fight Parkinson's disease and dementia with Lewy bodies: a pilot study"],"prefix":"10.3389","volume":"17","author":[{"given":"Tomasz","family":"Chmiela","sequence":"first","affiliation":[{"name":"Department of Neurology, Mayo Clinic","place":["Jacksonville, FL, Unites States"]},{"name":"Department of Neurology, Faculty of Medical Sciences, Medical University of Silesia","place":["Katowice, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Dulski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic","place":["Jacksonville, FL, Unites States"]},{"name":"Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdansk","place":["Gdansk, Poland"]},{"name":"Neurology Department, St Adalbert Hospital, Copernicus PL Ltd.","place":["Gdansk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Heckman","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics, Mayo Clinic","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui J.","family":"Fang","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics, Mayo Clinic","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew K.","family":"Wszolek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic","place":["Jacksonville, FL, Unites States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13024-025-00868-3","article-title":"Alpha-synuclein seeding amplification assays in Lewy body dementia: a brief review","volume":"20","author":"Bregendahl","year":"2025","journal-title":"Mol Neurodegener."},{"key":"B2","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/S1474-4422(23)00405-2","article-title":"A biological definition of neuronal \u03b1-synuclein disease: towards an integrated staging system for research","volume":"23","author":"Simuni","year":"2024","journal-title":"Lancet Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson's disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet."},{"key":"B4","volume-title":"Parkinson-Plus Syndrome","author":"Vertes","year":""},{"key":"B5","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.ncl.2024.12.009","article-title":"Disease-modifying therapies in Parkinson's disease","volume":"43","author":"Fabbri","year":"2025","journal-title":"Neurol Clin."},{"key":"B6","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.pneurobio.2016.10.001","article-title":"Insulin resistance and Parkinson's disease: a new target for disease modification?","volume":"146","author":"Athauda","year":"2016","journal-title":"Prog Neurobiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.3390\/antiox10121935","article-title":"Two birds one stone: the neuroprotective effect of antidiabetic agents on parkinson disease-focus on sodium-glucose cotransporter 2 (SGLT2) inhibitors","volume":"10","author":"Lin","year":"2021","journal-title":"Antioxidants."},{"key":"B8","doi-asserted-by":"publisher","first-page":"385","DOI":"10.5603\/pjnns.104405","article-title":"Parkinson's Disease and glucose dysregulation: shared pathophysiological mechanisms and clinical implications","volume":"59","author":"Chmiela","year":"2025","journal-title":"Neurol Neurochir Pol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"775","DOI":"10.3233\/JPD-191900","article-title":"The association between type 2 diabetes mellitus and parkinson's disease","volume":"10","author":"Cheong","year":"2020","journal-title":"J Parkinsons Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"917","DOI":"10.3233\/JPD-230104","article-title":"Diabetes and parkinson's disease: understanding shared molecular mechanisms","volume":"14","author":"K\u00f6nig","year":"2024","journal-title":"J Parkinsons Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"100265","DOI":"10.1016\/j.prdoa.2024.100265","article-title":"Antidiabetic drugs in Parkinson's disease","volume":"11","author":"Aguirre-Vidal","year":"2024","journal-title":"Clin Park Relat Disord."},{"key":"B12","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1080\/14728222.2022.2079492","article-title":"Therapeutic application of GLP-1 and GIP receptor agonists in Parkinson's disease","volume":"26","author":"Yang","year":"2022","journal-title":"Expert Opin Ther Targets."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1056\/NEJMoa2312323","article-title":"Trial of lixisenatide in early Parkinson's disease","volume":"390","author":"Meissner","year":"2024","journal-title":"N Engl J Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.neuropharm.2017.09.023","article-title":"Protective effects of the GLP-1 mimetic exendin-4 in Parkinson's disease","volume":"136","author":"Athauda","year":"2018","journal-title":"Neuropharmacology."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3067","DOI":"10.1093\/brain\/awaa262","article-title":"Diabetes medications and risk of Parkinson's disease: a cohort study of patients with diabetes","volume":"143","author":"Brauer","year":"2020","journal-title":"Brain."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1002\/mds.26734","article-title":"Reduced incidence of Parkinson's disease after dipeptidyl peptidase-4 inhibitors-A nationwide case-control study","volume":"31","author":"Svenningsson","year":"2016","journal-title":"Mov Disord."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e01029","DOI":"10.1002\/prp2.1029","article-title":"Suspected adverse drug reactions of the type 2 antidiabetic drug class dipeptidyl-peptidase IV inhibitors (DPP4i): can polypharmacology help explain?","volume":"10","author":"Jones","year":"2022","journal-title":"Pharmacol Res Perspect."},{"key":"B18","doi-asserted-by":"publisher","first-page":"107132","DOI":"10.1016\/j.parkreldis.2024.107132","article-title":"Anti-diabetic drug use and reduced risk of Parkinson's disease: a community-based cohort study","volume":"128","author":"Rozani","year":"2024","journal-title":"Parkinsonism Relat Disord."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.3390\/healthcare12232462","article-title":"Glucose metabolism disorders and Parkinson's disease: coincidence or indicator of dysautonomia?","volume":"12","author":"Chmiela","year":"2024","journal-title":"Healthcare."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1007\/s40120-025-00724-y","article-title":"Are glucagon-like peptide-1 (GLP-1) receptor agonists central nervous system (CNS) penetrant: a narrative review","volume":"14","author":"West","year":"2025","journal-title":"Neurol Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.1007\/s11357-024-01120-4","article-title":"Sitagliptin elevates plasma and CSF incretin levels following oral administration to nonhuman primates: relevance for neurodegenerative disorders","volume":"46","author":"Li","year":"2024","journal-title":"Geroscience."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3651","DOI":"10.3390\/ijms23073651","article-title":"An overview of the cardiorenal protective mechanisms of SGLT2 inhibitors","volume":"23","author":"Salvatore","year":"2022","journal-title":"Int J Mol Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.3390\/cells8091085","article-title":"Empagliflozin protects HK-2 cells from high glucose-mediated injuries via a mitochondrial mechanism","volume":"8","author":"Lee","year":"2019","journal-title":"Cells."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.14336\/AD.2020.1229","article-title":"The role of SGLT2 inhibitors in vascular aging","volume":"12","author":"Liu","year":"2021","journal-title":"Aging Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s40035-024-00431-y","article-title":"SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system","volume":"13","author":"Mei","year":"2024","journal-title":"Transl Neurodegener."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/mds.22340","article-title":"Movement disorder society-sponsored revision of the unified parkinson's disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results","volume":"23","author":"Goetz","year":"2008","journal-title":"Mov Disord."},{"key":"B27","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. a practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7213","DOI":"10.3390\/molecules26237213","article-title":"Neuroprotective effect of SGLT2 inhibitors","volume":"26","author":"Pawlos","year":"2021","journal-title":"Molecules."},{"key":"B29","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.parkreldis.2020.12.018","article-title":"Weight loss and weight gain in Parkinson disease","volume":"83","author":"Ghourchian","year":"2021","journal-title":"Parkinsonism Relat Disord."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.amjmed.2024.06.030","article-title":"Association between SGLT2 inhibitors and risk of dementia and Parkinson's disease: a meta-analysis of 12 randomized controlled trials","volume":"137","author":"Jaiswal","year":"2024","journal-title":"Am J Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s12325-022-02394-w","article-title":"GLP-1 agonists for weight loss: pharmacology and clinical implications","volume":"40","author":"Moore","year":"2023","journal-title":"Adv Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"338","DOI":"10.5603\/pjnns.100297","article-title":"Metabolic effects of deep brain stimulation in Parkinson's disease - a systematic review and meta-analysis","volume":"59","author":"Wegrzynek-Gallina","year":"2025","journal-title":"Neurol Neurochir Pol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.2337\/dc15-0355","article-title":"Energy balance after sodium-glucose cotransporter 2 inhibition","volume":"38","author":"Ferrannini","year":"2015","journal-title":"Diabetes Care."},{"key":"B34","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1161\/CIRCULATIONAHA.116.021887","article-title":"Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications","volume":"134","author":"Heerspink","year":"2016","journal-title":"Circulation."},{"key":"B35","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1056\/NEJMoa1501352","article-title":"Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes","volume":"373","author":"Green","year":"2015","journal-title":"N Engl J Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1210\/er.2014-1035","article-title":"Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors","volume":"35","author":"Mulvihill","year":"2014","journal-title":"Endocr Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.2337\/dc16-0330","volume":"39","year":"2016","journal-title":"Diabetes Care."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1038\/s41467-020-15983-6","article-title":"SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease","volume":"11","author":"Kim","year":"2020","journal-title":"Nat Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1161\/CIRCRESAHA.116.305665","article-title":"DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition","volume":"116","author":"Zhong","year":"2015","journal-title":"Circ Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1212\/WNL.48.1.119","article-title":"Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study","volume":"48","author":"Litvan","year":"1997","journal-title":"Neurology."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e209805","DOI":"10.1212\/WNL.0000000000209805","article-title":"SGLT2 inhibitor use and risk of dementia and Parkinson disease among patients with type 2 diabetes","volume":"103","author":"Kim","year":"2024","journal-title":"Neurology."},{"key":"B42","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s12264-017-0183-5","article-title":"Biomarkers for Parkinson's disease: recent advancement","volume":"33","author":"Lotankar","year":"2017","journal-title":"Neurosci Bull."},{"key":"B43","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/S1474-4422(19)30024-9","article-title":"CSF and blood biomarkers for Parkinson's disease","volume":"18","author":"Parnetti","year":"2019","journal-title":"Lancet Neurol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e35154","DOI":"10.7759\/cureus.33939","article-title":"Sodium-glucose cotransporter 2 (SGLT2) inhibitors: benefits versus risk","volume":"15","author":"Momin","year":"2023","journal-title":"Cureus."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.3389\/fphar.2024.1361651","article-title":"Dipeptidyl peptidase 4 inhibitors and their potential neuroprotective effects","volume":"101","author":"Ferrari","year":"2021","journal-title":"Physiol Rev."},{"key":"B46","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12883-018-1086-4","article-title":"Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy","volume":"18","author":"Erdogan","year":"2018","journal-title":"BMC Neurol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"147","DOI":"10.5603\/pjnns.98678","article-title":"Significance of dysautonomia in Parkinson's Disease and atypical parkinsonisms","volume":"58","author":"Alster","year":"2024","journal-title":"Neurol Neurochir Pol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"193","DOI":"10.5603\/pjnns.96939","article-title":"Comparison of autonomic dysfunction in patients with Parkinson's Disease, progressive supranuclear palsy, and multiple system atrophy","volume":"58","author":"Malkiewicz","year":"2024","journal-title":"Neurol Neurochir Pol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.parkreldis.2018.05.026","article-title":"Glucose dysregulation in Parkinson's disease: too much glucose or not enough insulin?","volume":"55","author":"Marques","year":"2018","journal-title":"Parkinsonism Relat Disord."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.2147\/DMSO.S359856","article-title":"If not Alpha-synuclein seeding amplification","volume":"15","author":"Chmiela","year":"2022","journal-title":"Diabetes Metab Syndr Obes."},{"key":"B51","doi-asserted-by":"publisher","first-page":"104700","DOI":"10.1016\/j.nbd.2019.104700","article-title":"Autonomic dysfunction in Parkinson's disease: Implications for pathophysiology, diagnosis, and treatment","volume":"134","author":"Chen","year":"2020","journal-title":"Neurobiol Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s10286-025-01146-4","article-title":"Prevalence and impact of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis","volume":"35","author":"Wang","year":"2025","journal-title":"Clin Auton Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.2337\/dc10-0612","article-title":"Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial","volume":"33","author":"Ferrannini","year":"2010","journal-title":"Diabetes Care."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1825229\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:29:02Z","timestamp":1780504142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1825229\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":53,"alternative-id":["10.3389\/fneur.2026.1825229"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1825229","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1825229"}}