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. 2025 May 2:16:1497261.
doi: 10.3389/fphar.2025.1497261. eCollection 2025.

Randomized, double-blind, placebo-controlled pilot study of metformin as an adjunctive therapy in Parkinson's disease

Hayam Ali AlRasheed  1 , Mostafa M Bahaa  2 , Thanaa A Elmasry  3   4 , Eman I Elberri  5 , Fedaa A Kotkata  5 , Ramy M El Sabaa  6 , Yasmine M Elmorsi  5 , Mostafa M Kamel  7 , Walaa A Negm  8 , Amir O Hamouda  9 , Khlood Mohammad Aldossary  1 , Muhammed M Salahuddin  9 , Mohamed Yasser  10   11   12 , Mamdouh Eldesouqui  10 , Manal A Hamouda  6 , Nashwa Eltantawy  13 , Mirna E Elawady  14 , Mahmoud S Abdallah  15   16
Affiliations

Randomized, double-blind, placebo-controlled pilot study of metformin as an adjunctive therapy in Parkinson's disease

Hayam Ali AlRasheed et al. Front Pharmacol. .

Abstract

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 3 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.

Clinical trial registration: identifier NCT05781711.

Keywords: Parkinson disease; TLR-4; metformin; neuro-inflammation; α-synuclein.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram showing the flow of patients during the study.
See this image and copyright information in PMC

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