Associations between long-term metformin use, the risk of vitamin B12 deficiency, and neuropathy: An All of Us research Program study

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-08-22 DOI:10.1016/j.diabres.2025.112424

Aryana Sepassi , Jiayuan Wang , Sophia Yankowski , Aya Enkoji , Mmeridi Okenwa , Candis M. Morello , Keri Hurley-Kim

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Abstract

Aims

The primary objective of this study is to investigate the associations between long-term metformin use, vitamin B12 status, and peripheral neuropathy. Secondarily, we aim to explore the effect of time since diagnosis on the relationships between metformin use, vitamin B12 deficiency, and peripheral neuropathy.

Methods

A retrospective observational cross-sectional analysis was conducted using NIH’s All of Us database. The risk of vitamin B12 deficiency and peripheral neuropathy was compared among long-term metformin users (≥4 years), short-term users (<4 years), and non-metformin users via a series of unadjusted and adjusted logistic regression models.

Results

Among 14,808 adults with type 2 diabetes mellitus (T2DM), 9,136 (61.70 %) used metformin, of whom 5,609 (37.95 %) were long-term users. Following adjustment for confounders, long-term users exhibited a 67 % and 38 % higher likelihood of vitamin B12 deficiency than non-users and short-term users respectively (p < 0.001). Peripheral neuropathy prevalence was 39 % higher among long-term users compared to short-term users (p < 0.001), with a non-statistically significant difference compared to non-users.

Conclusions

Long-term metformin use is associated with both an increased risk of vitamin B12 deficiency and peripheral neuropathy in patients with T2DM. Providers should consider routinely assessing vitamin B12 status in long-term users, particularly when evaluating peripheral neuropathy symptoms.

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长期使用二甲双胍、维生素B12缺乏风险和神经病变之间的关系：一项我们所有人的研究项目研究

目的：本研究的主要目的是调查长期使用二甲双胍、维生素B12状态和周围神经病变之间的关系。其次，我们的目的是探讨诊断后时间对二甲双胍使用、维生素B12缺乏症和周围神经病变之间关系的影响。方法采用美国国立卫生研究院All of Us数据库进行回顾性观察性横断面分析。通过一系列未调整和调整的logistic回归模型，比较长期二甲双胍使用者（≥4年）、短期二甲双胍使用者（<；4年）和非二甲双胍使用者维生素B12缺乏症和周围神经病变的风险。结果14808例成人2型糖尿病（T2DM）患者中，9136例（61.70%）使用二甲双胍，其中5609例（37.95%）长期使用。调整混杂因素后，长期服用者比不服用者和短期服用者分别表现出67%和38%的维生素B12缺乏症（p < 0.001）。长期服用者的周围神经病变患病率比短期服用者高39% (p < 0.001)，与非服用者相比差异无统计学意义。结论：长期使用二甲双胍与T2DM患者维生素B12缺乏和周围神经病变的风险增加有关。提供者应考虑常规评估长期使用者的维生素B12状态，特别是在评估周围神经病变症状时。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.