COMPARATIVE EFFECTS OF CURCUMIN AND METFORMIN CO-THERAPY VERSUS METFORMIN ALONE IN DIABETIC NEUROPATHY
Keywords:
Antioxidants, Curcumin, Diabetes Mellitus, Diabetic Neuropathies, , Metformin, Nerve Conduction, Oxidative StressAbstract
Background: Diabetic neuropathy is a major complication of diabetes mellitus characterized by progressive sensory loss and pain due to chronic hyperglycemia and oxidative stress. Metformin remains the standard antidiabetic therapy, but its effects on neuropathic complications are limited. Curcumin, a natural polyphenol with antioxidant and anti-inflammatory properties, has shown potential neuroprotective effects. Combining curcumin with metformin may provide synergistic benefits in mitigating neuropathic progression.
Objective: To determine whether curcumin supplementation enhances the neuroprotective efficacy of metformin in patients with diabetic neuropathy compared to metformin monotherapy.
Methods: A randomized controlled trial was conducted among 80 adults (aged 35–65 years) with type 2 diabetes and confirmed peripheral neuropathy in tertiary care hospitals of South Punjab. Participants were randomly assigned to receive either metformin alone (1000 mg twice daily) or metformin with curcumin (500 mg twice daily) for 16 weeks. Neuropathic symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) and Neuropathy Disability Score (NDS), while nerve conduction velocity (NCV), fasting blood glucose, glycated hemoglobin (HbA1c), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured pre- and post-intervention. Data were analyzed using paired and independent t-tests with a significance threshold of p < 0.05.
Results: Both groups showed improvement, but the combination group exhibited significantly greater reductions in MNSI (7.9 ± 1.2 to 4.9 ± 0.9) and NDS (5.7 ± 1.4 to 3.6 ± 1.0) scores, with marked increases in sural and peroneal NCV (p < 0.01). Curcumin co-therapy also resulted in superior glycemic control and reduced oxidative stress, reflected by decreased MDA and increased TAC levels.
Conclusion: Curcumin and metformin co-therapy demonstrated enhanced neuroprotective, metabolic, and antioxidant effects compared with metformin alone, suggesting a promising adjunctive approach for managing diabetic neuropathy.
References
1. Li H, Liu R, Liu J, Qu YJB. The role and mechanism of metformin in the treatment of nervous system diseases. 2024;14(12):1579.
2. Alrefaei AF, Elbeeh MEJB. Alpha-Lipoic Acid and Metformin Combination Therapy Synergistically Activate Nrf2-AMPK Signaling Pathways to Ameliorate Cognitive Dysfunction in Type 2 Diabetic Encephalopathy: A Preclinical Study. 2025;14(7):885.
3. Lin Q, Li K, Chen Y, Xie J, Wu C, Cui C, et al. Oxidative stress in diabetic peripheral neuropathy: pathway and mechanism-based treatment. 2023;60(8):4574-94.
4. Liu F, You F, Yang L, Wang S, Xie DJJoD, Complications i. Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress. 2024;38(6):108737.
5. Karami F, Jamaati H, Coleman-Fuller N, Zeini MS, Hayes AW, Gholami M, et al. Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis. 2023;75(3):511-43.
6. Xiaoqin S, Yi T, Xiaoyu L, Ya B, Jingwen S, Yin LJM. Research progress of traditional Chinese medicine monomer in treating diabetic peripheral neuropathy: a review. 2024;103(13):e37767.
7. Zhou Z, Luo G, Li C, Zhang P, Chen W, Li X, et al. Metformin induces M2 polarization via AMPK/PGC-1α/PPAR-γ pathway to improve peripheral nerve regeneration. 2023;15(5):3778.
8. Abozaid OA, Moawed FS, Gabr HF, Esmat MAJD-R. Combined Effects of Metformin, Quercetin, and Fractionated Gamma Irradiation on MiR-107-Mediated Brain Injury in HFD/STZ-Induced Diabetic Rats. 2025;23(3):15593258251367627.
9. Chen Y, Deng H, Zhang NJNRR. Autophagy-targeting modulation to promote peripheral nerve regeneration. 2025;20(7):1864-82.
10. Liu J, Li K, Yi Z, Saqirile, Wang C, Yang RJCIiMB. Oxidative–Inflammatory Crosstalk and Multi-Target Natural Agents: Decoding Diabetic Vascular Complications. 2025;47(8):614.
11. Rezaee A, Rahmanian P, Nemati A, Sohrabifard F, Karimi F, Elahinia A, et al. NF-ĸB axis in diabetic neuropathy, cardiomyopathy and nephropathy: A roadmap from molecular intervention to therapeutic strategies. 2024;10(9).
12. Liu X, Liang Q, Jiang W, Zhou J, Liu C, Deng L, et al. Curcumin and its novel formulations for diabetes mellitus and its complications: a review. 2025.
13. Zamanian MY, Giménez-Llort L, Nikbakhtzadeh M, Kamiab Z, Heidari M, Bazmandegan GJCMP. The therapeutic activities of metformin: focus on the Nrf2 signaling pathway and oxidative stress amelioration. 2023;16(3):331-45.
14. Eqbal A, Kushwaha P, Kumar S, Nisha A, Ahsan R, Asif MJE, et al. An Insight into the Therapeutic Potential of Phytobioactives for Diabetic Neuropathy. 2025;133(09):462-72.
15. Abd El-Emam MM, Behairy A, Mostafa M, Khamis T, Osman NM, Alsemeh AE, et al. Chrysin-loaded PEGylated liposomes protect against alloxan-induced diabetic neuropathy in rats: the interplay between endoplasmic reticulum stress and autophagy. 2024;57(1):45.
16. Alkholifi FK, Aodah AH, Foudah AI, Alam AJB. Exploring the Therapeutic Potential of Berberine and Tocopherol in Managing Diabetic Neuropathy: A Comprehensive Approach towards Alleviating Chronic Neuropathic Pain. 2023;11(6):1726.
17. Lehoczki A, Fekete M, Jarecsny T, Zábó V, Szappanos Á, Csípő T, et al. The Neuroprotective Role of Curcumin: From Molecular Pathways to Clinical Translation—A Narrative Review. 2025;17(17):2884.
18. Darenskaya M, Kolesnikov S, Semenova N, Kolesnikova LJIJoMS. Diabetic nephropathy: significance of determining oxidative stress and opportunities for antioxidant therapies. 2023;24(15):12378.
19. Jin Q, Liu T, Qiao Y, Liu D, Yang L, Mao H, et al. Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols. 2023;14:1185317.
20. Kropp M, Golubnitschaja O, Mazurakova A, Koklesova L, Sargheini N, Vo T-TKS, et al. Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation. 2023;14(1):21-42.
21. He W, Tang P, Lv HJFiI. Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches. 2025;16:1571576.
22. Sabari SS, Balasubramani K, Iyer M, Sureshbabu HW, Venkatesan D, Gopalakrishnan AV, et al. Type 2 diabetes (T2DM) and Parkinson’s disease (PD): a mechanistic approach. 2023;60(8):4547-73.
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Copyright (c) 2025 Atif Kaleem, Rabia Saleem (Author)
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