AlRasheed Hayam Ali, Bahaa Mostafa M, Elmasry Thanaa A, Elberri Eman I, Kotkata Fedaa A, El Sabaa Ramy M, Elmorsi Yasmine M, Kamel Mostafa M, Negm Walaa A, Hamouda Amir O, Aldossary Khlood Mohammad, Salahuddin Muhammed M, Yasser Mohamed, Eldesouqui Mamdouh, Hamouda Manal A, Eltantawy Nashwa, Elawady Mirna E, Abdallah Mahmoud S
Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt.
Front Pharmacol. 2025 May 2;16:1497261. doi: 10.3389/fphar.2025.1497261. eCollection 2025.
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.
This study aimed to clarify the role of metformin as adjuvant therapy in patients with PD.
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.
The improvement in UPDRS from baseline to 3 months.
Change in the level of biological markers.
The control group did not show significant difference in UPDRS when compared to their baseline value by Wilcoxon test ( > 0.05), meanwhile the metformin group showed significant difference when compared to before treatment by Wilcoxon test ( < 0.05). There were no significant differences between the two groups in UPDRS after treatment ( > 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 ( < 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.
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.
identifier NCT05781711.
帕金森病（PD）是由黑质中多巴胺能神经元的渐进性丧失引起的。神经炎症被认为是导致PD病理生理学的关键因素。目前PD的金标准疗法仅能缓解症状，无法减缓疾病进展，这凸显了开发新的疾病修饰治疗方法的必要性。二甲双胍已被证明在包括PD在内的几种神经退行性疾病中发挥神经保护作用。
本研究旨在阐明二甲双胍作为辅助治疗在PD患者中的作用。
60例PD患者分为2组（n = 30）。第1组患者每天3次服用左旋多巴/卡比多巴（250/25 mg），持续3个月，加用安慰剂（对照组），而第2组患者每天3次服用左旋多巴/卡比多巴（250/25 mg），每天2次服用500 mg二甲双胍（二甲双胍组）。通过统一帕金森病评定量表（UPDRS）对患者进行评估。在治疗前后测量血清中Toll样受体4（TLR-4）、α-突触核蛋白、脑源性神经营养因子（BDNF）和高迁移率族蛋白B1（HMGB-1）的浓度。
从基线到3个月时UPDRS的改善情况。
生物标志物水平的变化。
通过Wilcoxon检验，对照组与基线值相比，UPDRS无显著差异（> 0.05），同时，二甲双胍组与治疗前相比，通过Wilcoxon检验有显著差异（< 0.05）。通过Mann-Whitney检验，治疗后两组在UPDRS方面无显著差异（> 0.05）。然而，与基线和对照组相比，二甲双胍组的TLR-4、HMGB-1和α-突触核蛋白显著降低，BDNF有统计学意义的升高（< 0.05）。与基线相比，对照组所有标志物均无显著变化。
虽然二甲双胍组和对照组在UPDRS评分上没有观察到显著差异，但生物标志物变化趋势表明，辅助使用二甲双胍可能对PD的潜在病理生理学有影响。需要进一步研究以评估其在更长时间内对运动症状的影响。
标识符NCT05781711。
