Nickan Research Institute Immunopathologia Persa 2423-8015 12 1 2026 01 01 Efficacy of metformin in the treatment of parkinsonism and depression among diabetic patients type 2 e43986 e43986 10.34172/ipp.2025.43986 EN Waleed S. El Nasser https://orcid.org/0000-0001-9501-068X Eman M. Fahmy https://orcid.org/0000-0003-2385-9638 Ahmed M. Helmy https://orcid.org/0009-0005-0659-7017 Mohamed W. Saleh https://orcid.org/0009-0002-4980-0976 Amr Sherif Sherif Hassan https://orcid.org/0009-0005-0335-4845 Mahmoud Abdallah Mansour Abdelrahman https://orcid.org/0009-0005-7762-5169 Hamada H. Hassan https://orcid.org/0009-0008-9455-4210 Basem Abd El-Hamid https://orcid.org/0000-0002-0673-5919 Shimaa Fouad https://orcid.org/0009-0005-7056-9328 Mai Ali Mohammad Etewa https://orcid.org/0009-0001-0315-3710 Taha AM https://orcid.org/0009-0003-9467-649X Tayee Elsayed Mohamed https://orcid.org/0009-0002-3755-4456 Alaa Abo Seif https://orcid.org/0009-0007-5653-676X Ahmad Mohammad Mohammad Abdella https://orcid.org/0009-0005-9771-1785 Rashad Abd El-Nabi Atlam https://orcid.org/0009-0001-4306-6064 Nelly Hegazy https://orcid.org/0000-0002-3662-6238 Mohamed Ali Abbas https://orcid.org/0000-0003-4653-5687 Mohamed Y. Zeid https://orcid.org/0009-0003-1655-004X Kawashty R. Mohamed https://orcid.org/0009-0003-6043-8848 Abdelrahman Noureldeen https://orcid.org/0009-0001-0859-8276 Heba Kamel Badawy https://orcid.org/0000-0002-9791-1147 Journal Article 10.34172/ipp.2025.43986 2025 08 23 2025 11 21 Introduction: Parkinson’s disease (PD) often coexists with type 2 diabetes mellitus (T2DM), which may worsen disease progression. Metformin, a common diabetes medication, showed potential benefits beyond blood sugar control. Objectives: This study examines metformin’s impact on renal function, neurological biomarkers, and clinical outcomes in patients with both PD and T2DM. Patients and Methods: This prospective case-control study involved 50 patients with both T2DM and parkinsonism, recruited from Al-Azhar university hospitals in Assiut, Egypt, between August 2024 and August 2025. Participants were divided equally into two groups; a control group receiving their standard treatment for Parkinsonism and diabetes, and a metformin-treated group receiving metformin alongside their usual therapies. Demographic data and laboratory markers were collected at baseline. Disease assessment employed standardized tools such as the unified Parkinson’s Disease Rating Scale (UPDRS) for motor function, Beck Depression Inventory (BDI) for depression severity, Hoehn and Yahr scale for disease staging, Montreal Cognitive Assessment (MoCA) for cognitive evaluation, and Parkinson’s Disease Questionnaire-39 (PDQ-39) for quality of life (QOL). All assessments were repeated after a 12-month follow-up to analyze changes relative to baseline. Results: The findings indicated that metformin treatment offers comprehensive benefits by protecting against renal function decline, influencing neurological biomarkers, and supporting multiple clinical domains in PD. It appears to mitigate disease progression, preserve cognitive function, and enhance psychosocial well-being, while having neutral effects on vitamin status and potentially positive, though non-significant, effects on inflammatory markers. Overall, metformin not only prevents typical clinical deterioration but also actively improves motor, cognitive, psychological, and quality-of-life outcomes. Conclusion: Metformin demonstrates promising multifaceted benefits in PD patients with T2DM by not only protecting renal function and preventing clinical deterioration but also actively improving motor, cognitive, psychological, and quality-of-life outcomes across multiple clinical domains, supporting its consideration as an adjunctive therapeutic strategy pending further research.