---
title: "Type 2 Diabetes and Metformin Use in Parkinson’s Disease: Mendelian Randomization and Cohort Findi"
id: "pubmed-42627515"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42627515"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42627515/"
doi: "10.1007/s10072-026-09337-1"
published_at: "2026-08-21T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Type 2 Diabetes and Metformin Use in Parkinson’s Disease: Mendelian Randomization and Cohort Findi
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42627515
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42627515/)
- **DOI:** [10.1007/s10072-026-09337-1](https://doi.org/10.1007%2Fs10072-026-09337-1)
- **Published At:** 2026-08-21T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This study investigated causal relationships between **type 2 diabetes (T2D)**, **metformin** use, and risk of **Parkinson’s disease (PD)** using two complementary approaches: Mendelian randomization (MR) with GWAS summary data and pharmacovigilance analysis of FAERS reports. - MR analyses included univariable and multivariable approaches and sensitivity tests to assess robustness; multivariable MR (MVMR) estimated direct effects of T2D and metformin use on PD when accounting for each other. - In univariable MR, genetically predicted T2D showed no association with PD (OR 1.02, 95% CI 0.96–1.09, P = 0.47), while genetically proxied **metformin use** was associated with a modestly increased PD risk (OR 1.08, 95% CI 1.02–1.14, P = 0.011). - MVMR found opposite effects when both exposures were modeled together: **T2D** was associated with a decreased PD risk (OR 0.63, 95% CI 0.50–0.78, P = 5.09E-5) whereas **metformin use** showed a stronger association with increased PD risk (OR 1.63, 95% CI 1.31–2.03, P = 1.29E-5). - Pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) from 2004 Q1 to 2024 Q2 identified 179 reports of Parkinsonism among 228,283 metformin-related adverse event reports; reporting odds ratio (ROR) was 5.25, indicating a significant signal linking metformin use with Parkinsonism in spontaneous reports. - Authors conclude there are opposing causal signals for **T2D** and **metformin** on PD risk and emphasize consideration of potential adverse neurological effects of metformin in patients with or at risk for PD. - The study reanalyzed publicly available GWAS summary statistics; ethical approvals for original GWAS were previously granted and the authors declared no competing interests. Details of GWAS cohorts, instrument selection, and sensitivity-analysis specifics were not reported in the abstract.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. * 2 School of Systems Biology, George Mason University, Manassas, VA, 20110, USA. * 3 Research Centre for Medical Genetics, Moscow, 115478, Russia. * 4 Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. zfqeee@126.com. * 5 Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, China. zfqeee@126.com. # Contributed equally. * PMID: **42627515** * DOI: [ 10.1007/s10072-026-09337-1 ](https://doi.org/10.1007/s10072-026-09337-1) Item in Clipboard # Exploring the impacts of type 2 diabetes and metformin use on Parkinson's disease: Mendelian randomization analysis and a national cohort study Li Fu et al. Neurol Sci. 2026. Show details Display options Display options Format Abstract PubMed PMID Neurol Sci Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neurol+Sci%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Neurol+Sci%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) . 2026 Aug 21;47(9):726. doi: 10.1007/s10072-026-09337-1. ### Authors [Li Fu](https://pubmed.ncbi.nlm.nih.gov/?term=Fu+L&cauthor_id=42627515)[#](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-affiliation-1 "Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China."), [Hongbao Cao](https://pubmed.ncbi.nlm.nih.gov/?term=Cao+H&cauthor_id=42627515)[#](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-equal-contrib-explanation "Contributed equally")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-affiliation-2 "School of Systems Biology, George Mason University, Manassas, VA, 20110, USA."), [Ancha Baranova](https://pubmed.ncbi.nlm.nih.gov/?term=Baranova+A&cauthor_id=42627515)[#](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-equal-contrib-explanation "Contributed equally")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-affiliation-2 "School of Systems Biology, George Mason University, Manassas, VA, 20110, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-affiliation-3 "Research Centre for Medical Genetics, Moscow, 115478, Russia."), [Fuquan Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+F&cauthor_id=42627515)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-affiliation-4 "Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. zfqeee@126.com.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42627515/#short-view-affiliation-5 "Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, China. zfqeee@126.com.") ### Affiliations * 1 Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. * 2 School of Systems Biology, George Mason University, Manassas, VA, 20110, USA. * 3 Research Centre for Medical Genetics, Moscow, 115478, Russia. * 4 Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. zfqeee@126.com. * 5 Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, China. zfqeee@126.com. # Contributed equally. * PMID: **42627515** * DOI: [ 10.1007/s10072-026-09337-1 ](https://doi.org/10.1007/s10072-026-09337-1) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** The contribution of type 2 diabetes (T2D) and metformin use to Parkinson's disease (PD) remains unclear. This study aimed to investigate both the overall and independent effects of T2D and metformin use on PD risk. **Methods:** GWAS summary datasets were utilized for the Mendelian randomization (MR) analysis to explore the causal relationships between T2D, metformin use, and PD, complemented by sensitivity analyses to validate the robustness of the results. Multivariable MR (MVMR) was applied to assess the direct effects of T2D and metformin use on PD. Additionally, the FAERS database (2004 Q1-2024 Q2) was analyzed to elucidate the association of metformin use with Parkinsonism using the reporting odds ratio (ROR). **Results:** Our MR analysis showed T2D was not associated with the risk of PD (OR: 1.02, 95% CI: 0.96-1.09, P = 0.47), while metformin use was associated with an increased risk of PD (OR: 1.08, 95% CI: 1.02-1.14, P = 0.011). The MVMR analysis demonstrated that T2D was robustly associated with a decreased risk of PD (OR: 0.63, 95% CI: 0.50-0.78, P = 5.09E-5), while metformin use was linked to a higher risk of PD (OR: 1.63, 95% CI: 1.31-2.03, P = 1.29E-5). Using FAERS, a total of 179 cases of Parkinsonism were identified from 228,283 reports of metformin-related adverse events, indicating a significant association of metformin use with Parkinsonism (ROR: 5.25). **Conclusion:** Our study reveals opposing causal effects of T2D and metformin use on PD, emphasizing the need to consider metformin's potential adverse effects in PD patients. **Keywords:** Mendelian randomization; Metformin; Parkinson’s disease; Type 2 diabetes. © 2026. Fondazione Società Italiana di Neurologia. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethical approval: Ethical approval had been granted for each of the original GWAS studies. As our research only reanalyzed publicly released aggregated summary statistics, separate ethical approval was not required for the present work. Competing interests: The authors declare that they have no competing interests. Informed consent: Not applicable. ## References 1. 1. Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V (2022) Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol 22(11):657–673 - [DOI](https://doi.org/10.1038/s41577-022-00684-6) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35246670/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8895080/) 2. 1. Ben-Shlomo Y, Darweesh S, Llibre-Guerra J, Marras C, San Luciano M, Tanner C (2024) The epidemiology of Parkinson’s disease. Lancet 403(10423):283–292 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38245248/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/11123577/) - [DOI](https://doi.org/10.1016/s0140-6736\(23\)01419-8) 3. 1. Wang Y, Shi X, Yin Y et al (2024) Association between neuroinflammation and Parkinson’s disease: a comprehensive Mendelian randomization study. Mol Neurobiol 61(12):10216–10226 - [DOI](https://doi.org/10.1007/s12035-024-04197-2) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38709392/) 4. 1. Mai AS, Tan BJ, Sun QY, Tan EK (2024) Association between type 1 diabetes mellitus and Parkinson’s disease: a Mendelian randomization study. J Clin Med. - [DOI](https://doi.org/10.3390/jcm13020561) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/39274429/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/11396206/) 5. 1. Paul KC, Zhang K, Walker DI et al (2023) Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson’s disease. Mol Neurodegener 18(1):100 - [DOI](https://doi.org/10.1186/s13024-023-00694-5) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38115046/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10731845/) Show all 93 references ## MeSH terms * Cohort Studies Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cohort+Studies%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cohort+Studies) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Diabetes Mellitus, Type 2* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Diabetes Mellitus, Type 2* / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fepidemiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Diabetes Mellitus, Type 2* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Genome-Wide Association Study Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Genome-Wide+Association+Study%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Genome-Wide+Association+Study) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Hypoglycemic Agents* / adverse effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Hypoglycemic+Agents%2Fadverse+effects%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Hypoglycemic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Hypoglycemic Agents* / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Hypoglycemic+Agents%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Hypoglycemic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Mendelian Randomization Analysis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mendelian+Randomization+Analysis%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mendelian+Randomization+Analysis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Metformin* / adverse effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Metformin%2Fadverse+effects%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Metformin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Metformin* / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Metformin%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Metformin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Parkinson Disease* / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Parkinson+Disease%2Fepidemiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Parkinson+Disease) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627515/) * Parkinson Disease* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Parkinson+Disease%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search
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