AN OBSERVATIONAL STUDY OF PERIPHERAL NEUROPATHY IN DIABETES PATIENTS ON METFORMIN THERAPY AND THE ROLE OF VITAMIN B-12 SUPPLEMENTATION

HARITHA PASUPULATI; BODDUPALLY SWATHI; SAMEENA TAHSEEN; MOHAMMED SHAHZAIB ANWER; R. SANDHYA; SAMREEN FATHIMA; SYEDA AMARA FATIMA

doi:10.22159/ijpps.2024v16i12.52405

Authors

HARITHA PASUPULATI Department of Pharmacology, Bharat School of Pharmacy, Mangalpally, Ibrahimpatnam, Hyderabad, India https://orcid.org/0000-0002-6121-5502
BODDUPALLY SWATHI Department of Pharm. D, Bharat School of Pharmacy, Mangalpally, Ibrahimpatnam, Hyderabad, India
SAMEENA TAHSEEN Bharat School of Pharmacy, Mangalpally, Ibrahimpatnam Hyderabad, India https://orcid.org/0009-0003-4732-4678
MOHAMMED SHAHZAIB ANWER Department of Pharm. D, Bharat School of Pharmacy, Mangalpally, Ibrahimpatnam, Hyderabad, India
R. SANDHYA Department of Bio Technology, Bharat School of Pharmacy, Mangalpally, Ibrahimpatnam, Hyderabad, India
SAMREEN FATHIMA Department of Pharm. D, Bharat School of Pharmacy, Mangalpally, Ibrahimpatnam, Hyderabad, India
SYEDA AMARA FATIMA Department of Pharm. D, Bharat School of Pharmacy, Mangalpally, Ibrahimpatnam, Hyderabad, India

DOI:

https://doi.org/10.22159/ijpps.2024v16i12.52405

Keywords:

Peripheral neuropathy, diabetes, metformin therapy, vitamin B-12 supplementation, vitamin B-12 deficiency, dosage correlation, metformin duration

Abstract

Objective: This study aims to assess the prevalence of peripheral neuropathy in diabetic patients on metformin therapy using the Douleur Neuropathique 4 (DN-4) scale, explore the relationship between long-term metformin use and serum vitamin B-12 levels, and identify how metformin contributes to neuropathy. Additionally, it seeks to raise awareness about the importance of vitamin B-12 monitoring and supplementation for improving patient quality of life.

Methods: An observational study was conducted involving diabetes patients on metformin therapy. Data were collected on patient demographics, clinical characteristics, and vitamin B-12 levels. Peripheral neuropathy was assessed using the DN-4 questionnaire. Correlations between metformin duration, dosage, vitamin B-12 levels, and neuropathy prevalence were analyzed.

Results: The results indicated that the majority of the study population were male (61.2%) and aged 51-60 years (41.8%), with a majority proportion residing in urban areas (74%). A significant finding was that Peripheral neuropathy was prevalent in 44.8% of patients, with 51.5% exhibiting vitamin B-12 deficiency. Furthermore, the study identified a high prevalence of peripheral neuropathy with a significant correlation between longer metformin use and increased neuropathy (r =0.9372), additionally, a strong negative correlation between metformin dosage and Vitamin B-12 levels (r=-0.9189) highlighted the risk of deficiency with higher doses.

Conclusion: The study underscores the critical role of monitoring and supplementing vitamin B-12 in diabetes patients on metformin therapy to mitigate peripheral neuropathy. Regular screening and proactive supplementation could potentially reduce neuropathic complications associated with long-term metformin use.

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References

American Diabetes Association. Standards of medical care in diabetes; 2013. Diabetes Care. 2013 Jan;36 Suppl 1:S11-66. doi: 10.2337/dc13-S011, PMID 23264422.

Leon BM, Maddox TM. Diabetes and cardiovascular disease: epidemiology biological mechanisms treatment recommendations and future research. World J Diabetes. 2015;6(13):1246-58. doi: 10.4239/wjd.v6.i13.1246, PMID 26468341.

Senthilkumar N, Anandhasayanam A, Mohammed Safil K, Shemimol S. A comparative study on the effectiveness of angiotensin converting enzyme inhibitors (ACEIS) and angiotensin receptor blockers (ARBS) in diabetic nephropathy in type 2 diabetes mellitus patients. Int J Pharm Pharm Sci. 2016;8(8):289-92.

Wei J, Wei Y, Huang M, Wang P, Jia S. Is metformin a possible treatment for diabetic neuropathy? J Diabetes. 2022;14(10):658-69. doi: 10.1111/1753-0407.13310, PMID 36117320.

Selvarajah D, Kar D, Khunti K, Davies MJ, Scott AR, Walker J. Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention. Lancet Diabetes Endocrinol. 2019;7(12):938-48. doi: 10.1016/S2213-8587(19)30081-6, PMID 31624024.

Chowdary Dl N, IS. Prevalence and impact of painful diabetic peripheral neuropathy in patients with type 2 diabetes mellitus with low economic status. Asian J Pharm Clin Res. 2018;11(6):377-80. doi: 10.22159/ajpcr.2018.v11i6.21752.

Shahwan M, Hassan N, Noshi A. Prevalence and risk factors of vitamin B12 deficiency among patients with type II diabetes on metformin: a study from the northern region of United Arab Emirates. Asian J Pharm Clin Res. 2018;11(8):225-29. doi: 10.22159/ajpcr.2018.v11i8.26052.

DE Groot Kamphuis DM, Van Dijk PR, Groenier KH, Houweling ST, Bilo HJ, Kleefstra N. Vitamin B12 deficiency and the lack of its consequences in type 2 diabetes patients using metformin. Neth J Med. 2013;71(7):386-90. PMID 24038568.

Infante M, Leoni M, Caprio M, Fabbri A. Long-term metformin therapy and vitamin B12 deficiency: an association to bear in mind. World J Diabetes. 2021;12(7):916-31. doi: 10.4239/wjd.v12.i7.916, PMID 34326945.

Pratama S, Lauren BC, Wisnu W. The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: a systematic review. Diabetes Metab Syndr Syndr. 2022;16(10):102634. doi: 10.1016/j.dsx.2022.102634, PMID 36240684.

Gupta K, Jain A, Rohatgi A. An observational study of vitamin B12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy. Diabetes Metab Syndr Syndr. 2018;12(1):51-8. doi: 10.1016/j.dsx.2017.08.014, PMID 28882470.

Didangelos T, Karlafti E, Kotzakioulafi E, Margariti E, Giannoulaki P, Batanis G. Vitamin B12 supplementation in diabetic neuropathy: a 1-year randomized double-blind placebo controlled trial. Nutrients. 2021;13(2):395. doi: 10.3390/nu13020395, PMID 33513879.

Alharbi TJ, Tourkmani AM, Abdelhay O, Alkhashan HI, Al Asmari AK, Bin Rsheed AM. The association of metformin use with vitamin B12 deficiency and peripheral neuropathy in Saudi individuals with type 2 diabetes mellitus. PLOS ONE. 2018;13(10):e0204420. doi: 10.1371/journal.pone.0204420, PMID 30321183.

Miranda Massari JR, Gonzalez MJ, Jimenez FJ, Allende Vigo MZ, Duconge J. Metabolic correction in the management of diabetic peripheral neuropathy: improving clinical results beyond symptom control. Curr Clin Pharmacol. 2011;6(4):260-73. doi: 10.2174/157488411798375967, PMID 22082324.

Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Med (Baltim). 2019;98(46):e17918. doi: 10.1097/MD.0000000000017918, PMID 31725641.

KO SH, KO SH, Ahn YB, Song KH, Han KD, Park YM. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J Korean Med Sci. 2014;29(7):965-72. doi: 10.3346/jkms.2014.29.7.965, PMID 25045229.

Farooq MD, Tak FA, Ara F, Rashid S, Mir IA. Vitamin B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes. J Xenobiot. 2022;12(2):122-30. doi: 10.3390/jox12020011, PMID 35736024.

Al Quran T, Khader A, Allan H, Al Momani R, Aqel HT, Alsaleh M. Prevalence of vitamin B12 deficiency in type 2 diabetic patients taking metformin a cross-sectional study in primary healthcare. Front Endocrinol (Lausanne). 2023;14:1226798. doi: 10.3389/fendo.2023.1226798, PMID 37732117.

Al Zoubi MS, Al Kreasha R, Aqel S, Saeed A, Al Qudimat AR, Al Zoubi RM. Vitamin B12 deficiency in diabetic patients treated with metformin: a narrative review. Ir J Med Sci. 2024;193(4):1827-35. doi: 10.1007/s11845-024-03634-4, PMID 38381379.

Yang R, YU H, WU J, Chen H, Wang M, Wang S. Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing China. Front Endocrinol (Lausanne). 2023;14:1082720. doi: 10.3389/fendo.2023.1082720, PMID 36926032.

Alvarez M, Sierra OR, Saavedra G, Moreno S. Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study. Endocr Connect. 2019;8(10):1324-9. doi: 10.1530/EC-19-0382, PMID 31518991.