Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study

doi:10.1002/mds.29992

. 2024 Nov;39(11):1960-1970.

doi: 10.1002/mds.29992. Epub 2024 Aug 27.

Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study

Huilin Tang¹, Ying Lu¹, Michael S Okun², William T Donahoo³, Adolfo Ramirez-Zamora², Fei Wang⁴, Yu Huang⁵, Melissa Armstrong², Mikael Svensson^{1

6}, Beth A Virnig⁷, Steven T DeKosky^{8

9}, Jiang Bian⁵, Jingchuan Guo^{1

6}

Affiliations

¹ Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.
² Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida College of Medicine, Gainesville, Florida, USA.
³ Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Florida, Gainesville, Florida, USA.
⁴ Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, New York, USA.
⁵ Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA.
⁶ Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA.
⁷ College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA.
⁸ Department of Neurology and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida, USA.
⁹ 1Florida Alzheimer's Disease Research Center (ADRC), University of Florida, Gainesville, Florida, USA.

PMID: 39189078
PMCID: PMC11568939 (available on 2025-11-01)
DOI: 10.1002/mds.29992

Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study

Huilin Tang et al. Mov Disord. 2024 Nov.

. 2024 Nov;39(11):1960-1970.

doi: 10.1002/mds.29992. Epub 2024 Aug 27.

Authors

Affiliations

¹ Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.
² Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida College of Medicine, Gainesville, Florida, USA.
³ Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Florida, Gainesville, Florida, USA.
⁴ Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, New York, USA.
⁵ Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA.
⁶ Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA.
⁷ College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA.
⁸ Department of Neurology and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida, USA.
⁹ 1Florida Alzheimer's Disease Research Center (ADRC), University of Florida, Gainesville, Florida, USA.

PMID: 39189078
PMCID: PMC11568939 (available on 2025-11-01)
DOI: 10.1002/mds.29992

Abstract

Background: Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results.

Objective: The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D).

Methods: Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)-adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users.

Results: This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA.

Conclusion: Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; dipeptidyl peptidase 4 inhibitor (DPP4i); glucagon‐like peptide‐1 receptor agonist (GLP‐1RA); type 2 diabetes.

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Conflict of interest statement

Relevant conflicts of interest/financial disclosure: The authors declare no conflicts of interest relevant to this work.

References

1. Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368–376. doi:10.1136/jnnp.2007.131045 - DOI - PubMed
1. Yang W, Hamilton JL, Kopil C, et al. Current and projected future economic burden of Parkinson’s disease in the U.S. NPJ Park Dis. 2020;6:15. doi:10.1038/s41531-020-0117-1 - DOI - PMC - PubMed
1. Parkinson’s Disease: Challenges, Progress, and Promise | National Institute of Neurological Disorders and Stroke. Accessed November 27, 2023. https://www.ninds.nih.gov/current-research/focus-disorders/parkinsons-di...
1. Sabari SS, Balasubramani K, Iyer M, et al. Type 2 Diabetes (T2DM) and Parkinson’s Disease (PD): a Mechanistic Approach. Mol Neurobiol. 2023;60(8):4547–4573. doi:10.1007/s12035-023-03359-y - DOI - PMC - PubMed
1. Kleinridders A, Cai W, Cappellucci L, et al. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci U S A. 2015;112(11):3463–3468. doi:10.1073/pnas.1500877112 - DOI - PMC - PubMed

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[1] Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368–376. doi:10.1136/jnnp.2007.131045 - DOI - PubMed

[2] Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368–376. doi:10.1136/jnnp.2007.131045 - DOI - PubMed

[3] Yang W, Hamilton JL, Kopil C, et al. Current and projected future economic burden of Parkinson’s disease in the U.S. NPJ Park Dis. 2020;6:15. doi:10.1038/s41531-020-0117-1 - DOI - PMC - PubMed

[4] Yang W, Hamilton JL, Kopil C, et al. Current and projected future economic burden of Parkinson’s disease in the U.S. NPJ Park Dis. 2020;6:15. doi:10.1038/s41531-020-0117-1 - DOI - PMC - PubMed

[5] Parkinson’s Disease: Challenges, Progress, and Promise | National Institute of Neurological Disorders and Stroke. Accessed November 27, 2023. https://www.ninds.nih.gov/current-research/focus-disorders/parkinsons-di...

[6] Parkinson’s Disease: Challenges, Progress, and Promise | National Institute of Neurological Disorders and Stroke. Accessed November 27, 2023. https://www.ninds.nih.gov/current-research/focus-disorders/parkinsons-di...

[7] Sabari SS, Balasubramani K, Iyer M, et al. Type 2 Diabetes (T2DM) and Parkinson’s Disease (PD): a Mechanistic Approach. Mol Neurobiol. 2023;60(8):4547–4573. doi:10.1007/s12035-023-03359-y - DOI - PMC - PubMed

[8] Sabari SS, Balasubramani K, Iyer M, et al. Type 2 Diabetes (T2DM) and Parkinson’s Disease (PD): a Mechanistic Approach. Mol Neurobiol. 2023;60(8):4547–4573. doi:10.1007/s12035-023-03359-y - DOI - PMC - PubMed

[9] Kleinridders A, Cai W, Cappellucci L, et al. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci U S A. 2015;112(11):3463–3468. doi:10.1073/pnas.1500877112 - DOI - PMC - PubMed

[10] Kleinridders A, Cai W, Cappellucci L, et al. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci U S A. 2015;112(11):3463–3468. doi:10.1073/pnas.1500877112 - DOI - PMC - PubMed

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Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study

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Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study

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