Metformin is the most widely used antihyperglycemic drug in patients with type 2 diabetes (T2D). Over the past 2 decades, several studies have highlighted a substantial increase in the risk of vitamin B12 deficiency in patients with T2D on metformin therapy. This can lead to several complications and induce or exacerbate peripheral neuropathy. Despite these data, there are no definite guidelines for screening, diagnosing, and treating vitamin B12 deficiency in patients with T2D on metformin therapy. Therefore, in this narrative review, we aimed to suggest a practical diagnostic and therapeutic strategy to address vitamin B12 deficiency in patients with T2D receiving metformin treatment. Clinical evidence supporting an increased risk of vitamin B12 deficiency in patients with T2D on metformin therapy and its risk factors and potential complications are also discussed.
Citations
Citations to this article as recorded by
Correlation between vitamin B12 deficiency and hemoglobin A1c in patients with diabetes mellitus Yahya Madkhali, Sami G. Almalki Journal of King Saud University – Science.2025; 37: 3542024. CrossRef
Rethinking about Metformin: Promising Potentials Kyunam Kim Korean Journal of Family Medicine.2024; 45(5): 258. CrossRef
Prevalence of Vitamin B12 Deficiency in Patients With Type 2 Diabetes Mellitus on Metformin Therapy: A Cross-Sectional Study Shoaib Asghar, Haider Tanvir, Asad Riaz, Muhammad Hamza Ejaz, Mamuna Akram, Al Muktadir Chowdhury Evan, Salman Shahid Cureus.2024;[Epub] CrossRef
Background The role of uric acid in the development of diabetic peripheral neuropathy remains unclear. This study aimed to determine the association between uric acid and peripheral neuropathy among type 2 diabetes mellitus (T2DM) patients.
Methods We conducted a nationwide cross-sectional study based on the diabetes and hypertension study of the Medical Research Network of the Consortium of Thai Medical Schools. Adult T2DM patients from 831 public hospitals in Thailand were evaluated. The serum uric acid level was categorized into five groups based on quintiles (<4.4, 4.4–5.3, 5.3–6.2, 6.2–7.3, and >7.3 mg/dL). A multivariate logistic regression model was used to assess the independent association between serum uric acid level and peripheral neuropathy.
Results In total, 7,511 T2DM patients with available data about serum uric acid levels were included in the analysis. The mean age of the participants was 61.7±10.9 years, and approximately 35.6% were men. The prevalence rate of peripheral neuropathy was 3.0%. Moreover, the prevalence rates of peripheral neuropathy stratified according to uric acid levels <4.4, 4.4–5.3, 5.3–6.2, 6.2–7.3, and >7.3 mg/dL were 2.5%, 2.8%, 2.4%, 2.5%, and 4.7%, respectively. A serum uric acid level ≥7.3 mg/dL was found to be associated with an increase in odds ratio (1.54; 95% confidence interval, 1.02–2.32) for peripheral neuropathy compared with a serum uric acid level <4.4 mg/dL.
Conclusion Serum uric acid level is independently associated with peripheral neuropathy in T2DM patients, and elevated serum uric acid levels should be considered a risk factor for diabetic peripheral neuropathy in clinical practice.
Citations
Citations to this article as recorded by
Uric acid in diabetic microvascular complications: Mechanisms and therapy Xin Li, Bo Huang, Yue Liu, Meng Wang, Jing-Qiu Cui Journal of Diabetes and its Complications.2025; 39(2): 108929. CrossRef
Causality between serum uric acid and diabetic microvascular complications - a mendelian randomization study Hongli Wu, Xuefeng Li, Wenning Zhang, Huifang Peng, Hongwei Jiang Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef
Association between serum uric acid levels and diabetic peripheral neuropathy in type 2 diabetes: a systematic review and meta-analysis Xieyu Zhang, Xinwen Zhang, Xiaoxu Li, Xin Zhao, Guangcheng Wei, Jinjie Shi, Yue Yang, Su Fan, Jiahe Zhao, Ke Zhu, Jieyang Du, Junyi Guo, Wei Cao Frontiers in Endocrinology.2024;[Epub] CrossRef
Comparison of Serum Uric Acid-to-HDL Ratio and Triglyceride Glucose Index in Relation to Glycemic Control Among Patients with Type 2 Diabetes Mellitus Hafiza Farah Masood, Qurratul Ain, Hifza Noor Lodhi, Bilal Rafique Malik, Faheem Usman Sulehri, . Khushbakht, Mirza Zeeshan Sikandar, Sharoona Fatima Pakistan Journal of Health Sciences.2024; : 130. CrossRef
Serum uric acid and diabetic peripheral neuropathy: a double-edged sword Yong Zhuang, Huibin Huang, Xin Hu, Jinying Zhang, Qingyan Cai Acta Neurologica Belgica.2023; 123(3): 857. CrossRef
The Ratio of Serum Uric Acid to Glycosylated Haemoglobin as a Predictor of All-Mortality in Elderly Patients with Diabetic Foot Ulcers: A Longitudinal Cohort Study Xiuxian Huang, Licai Deng, Jianhao Huang, Jingxia Sun, Qiu Wang, Jiacheng Mo, Zhenwei Zhai, Yuechou Nong, Wensheng Lu Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 2779. CrossRef
Uric acid and diabetes mellitus: an update Shailendra K Singh, Rina Singh, Santosh K Singh, Mir A Iquebal, Sarika Jaiswal, Pradeep K Rai Postgraduate Medical Journal.2023; 99(1178): 1220. CrossRef
Serum uric acid and risk of diabetic neuropathy: a genetic correlation and mendelian randomization study Youqian Zhang, Zitian Tang, Ling Tong, Yang Wang, Lin Li Frontiers in Endocrinology.2023;[Epub] CrossRef
The relation between serum uric acid levels and diabetic peripheral neuropathy in type 2 diabetes in Guilan, north of Iran Haniye Sadat Fayazi, Maryam Yaseri, Seyyede Sahere Mortazavi, Zahra Sharifhassan, Ali-Sina Assadinia BMC Endocrine Disorders.2022;[Epub] CrossRef
Prevalence and Risk Factors for Peripheral Neuropathy in Chinese Patients With Gout Kaifeng Guo, Nan Liang, Mian Wu, Lihui Chen, Haibing Chen Frontiers in Neurology.2022;[Epub] CrossRef
Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy WeiZheng So, NatalieShi Qi Wong, HongChang Tan, MollyTzu Yu Lin, IsabelleXin Yu Lee, JodhbirS Mehta, Yu-Chi Liu Neural Regeneration Research.2022; 17(10): 2172. CrossRef
Sodium Glucose Cotransporter-2 Inhibitor Protects Against Diabetic Neuropathy and Nephropathy in Modestly Controlled Type 2 Diabetes: Follow-Up Study Fukashi Ishibashi, Aiko Kosaka, Mitra Tavakoli Frontiers in Endocrinology.2022;[Epub] CrossRef
The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study Yimeng Hu, Qinge Li, Rui Min, Yingfeng Deng, Yancheng Xu, Ling Gao PeerJ.2021; 9: e10691. CrossRef
Yon Su Kim, Be Long Cho, Woo Sik Kim, Sang Hyun Kim, In Hyeon Jung, Won Yong Sin, Dong Hoon Choi, Sang Jae Lee, Chun Soo Lim, Kyung Pyo Kang, Byung Yeon Yu, Wonju Jeung, Chang Gyu Park
Korean J Fam Med 2019;40(4):212-219. Published online July 20, 2019
Background We assessed the frequency and severity of hypoglycemia in type 2 diabetes mellitus patients treated with sulfonylurea monotherapy or sulfonylurea+metformin.
Methods We conducted a retrospective, observational, cross-sectional study in 2011 and 2012 including patients with type 2 diabetes mellitus aged ≥30 years who were treated with ≥6 months of sulfonylurea monotherapy or sulfonylurea+metformin at 20 university-affiliated hospitals in Korea. At enrollment, glycated hemoglobin (HbA1c) was assessed; participants completed self-reported questionnaires describing hypoglycemia incidents over the past 6 months. A review of medical records up to 12 months before enrollment provided data on demographics, disease history, comorbidities, laboratory results, and drug usage.
Results Of 726 enrolled patients, 719 were included (55.6% male); 31.7% and 68.3% were on sulfonylurea monotherapy and sulfonylurea+metformin, respectively. Mean±standard deviation age was 65.9±10.0 years; mean HbA1c level was 7.0%±1.0%; 77.8% of patients had hypertension (89.4% used antihypertensive medication); 60.5% had lipid disorders (72.5% used lipid-lowering medication); and 52.0% had one or more micro- or macrovascular diseases. Among patients with A1c measurement (n=717), 56.4% achieved therapeutic goals (HbA1c <7.0%); 42.4% (305/719) experienced hypoglycemia within 6 months of enrollment; and 38.8%, 12.9%, 12.7%, and 3.9% of patients experienced mild, moderate, severe, and very severe hypoglycemia symptoms, respectively. Several reported hypoglycemia frequency as 1–2 times over the last 6 months. The mean number of very severe hypoglycemia episodes was 3.5±5.5.
Conclusion Among type 2 diabetes mellitus patients treated with sulfonylurea-based regimens, glycemic levels were relatively well controlled but hypoglycemia remained a prevalent side effect.
Citations
Citations to this article as recorded by
Increasing Individual Target Glucose Levels to Prevent Hypoglycemia in Patients with Diabetes Juyoung Shin, Hyunah Kim, Hun-Sung Kim, Churlmin Kim, Whan-Seok Choi Korean Journal of Family Medicine.2021; 42(4): 269. CrossRef
Professional Continuous Glucose Monitoring Reveals Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease Treated with Oral Antidiabetics Maja Baretić, Valerija Bralić Lang Korean Journal of Family Medicine.2021; 42(2): 185. CrossRef
Exercise Strategies to Prevent Hypoglycemia in Patients with Diabetes Ah Reum Jung, Hyunah Kim, Hun-Sung Kim, Churlmin Kim, Whan-Seok Choi Korean Journal of Family Medicine.2021; 42(2): 91. CrossRef
First
Prev
