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CLINICAL TRIAL article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1497261
This article is part of the Research TopicEmerging Horizons of Metformin: Exploring Recent Advances and Addressing Challenges in Research and Clinical UtilizationView all 8 articles
Randomized, Double-blind, Placebo-Controlled Pilot Study of Metformin as an Adjunctive Therapy in Parkinson's disease
Provisionally accepted
Mostafa Bahaa1*
Hayam Ali Alrasheed2Thanaa A Elmasry3Eman I Elberri3Fedaa A Kotkata4Ramy M El Sabaa5Yasmine M Elmorsi4Mostafa M Kamel4Walaa A Negm4Amir O Hamouda1Khlood Mohammad Aldossary2Muhammed M Salahuddin6Mohamed Yasser6Mamdouh Eldesouqui7Manal A Hamouda5Nashwa Eltantawy8Mahmoud S Abdallah9- 1Faculty of Pharmacy, Horus University, Damietta, Egypt
- 2Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
- 3Faculty of Pharmacy, Tanta University, Tanta, Gharbia, Egypt
- 4Tanta University, Tanta, Gharbia, Egypt
- 5University of Menoufia, Shibin Al Kawm, Al Minufiyah, Monufia, Egypt
- 6Horus University, Damietta, Egypt
- 7Mansoura University, Mansoura, Dakahlia, Egypt
- 8Heliopolis University, Cairo, Beni Suef, Egypt
- 9Jadara University, Irbid, Irbid, Jordan
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Background: Parkinson's disease (PD) is caused by the progressive loss of dopaminergic neurons in the substantia nigra. Neuroinflammation is considered a key factor contributing to the pathophysiology of PD. Current gold-standard therapies for PD provide only symptomatic relief without slowing disease progression, highlighting the need to develop new disease-modifying treatments. Metformin has been demonstrated to exert a neuroprotective role in several neurodegenerative disorders including PD. Aim: This study aimed to clarify the role of metformin as adjuvant therapy in patients with PD. Methods: Sixty patients with PD were divided into 2 groups (n=30). Patients in group 1 received levodopa/carbidopa (250/25 mg) three times daily for three months plus placebo (Control group), while those in group 2 received levodopa/carbidopa (250/25 mg) three times daily and 500 mg metformin two times daily (Metformin group). Patients were assessed via Unified Parkinson's Disease Rating Scale (UPDRS). The serum concentrations of toll like receptor 4 (TLR-4), α-synuclein, brain derived neurotropic factor (BDNF), and high mobility group box 1 (HMGB-1) were measured before and after treatment. Primary outcome:The improvement in UPDRS from baseline to 3 months. Secondary outcome: Change in the level of biological markers. Results: The control group did not show significant difference in UPDRS when compared to their baseline value by Wilcoxon test (P > 0.05), meanwhile the metformin group showed significant difference when compared to before treatment by Wilcoxon test (P < 0.05). There were no significant differences between the two groups in UPDRS after treatment (P > 0.05) by Man Whitney test. However, the metformin group showed a significant decrease in TLR-4, HMGB-1, and α-synuclein along with a statistically significant increase in BDNF (P < 0.05) when compared to its baseline and control group. The control group did not show any significant changes in all markers when compared to their baseline. Conclusion: While no significant differences in UPDRS scores were observed between the metformin and control groups, trends in biomarker changes suggest a potential impact of adjunctive metformin use on the underlying pathophysiology of PD. Further studies are needed to assess its effects on motor symptoms over a longer duration.
Keywords: Parkinson Disease, Metformin, Neuro-inflammation, α-Synuclein, TLR-4
Received: 16 Sep 2024; Accepted: 14 Apr 2025.
Copyright: © 2025 Bahaa, Alrasheed, Elmasry, Elberri, Kotkata, El Sabaa, Elmorsi, Kamel, Negm, Hamouda, Aldossary, Salahuddin, Yasser, Eldesouqui, Hamouda, Eltantawy and Abdallah. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mostafa Bahaa, Faculty of Pharmacy, Horus University, Damietta, Egypt
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.