口服降血糖藥物二甲雙胍（Metformin）引起之維生素B12缺乏症

Metformin-Induced Vitamin B12 Deficiency

徐莞嘉(Wan-Chia Hsu) ； 陳榮福(Jung-Fu Chen) ； 沈峰志(Feng-Chih Shen)

《內科學誌》 31卷4期 (2020/08) Pp. 266-275

https://doi.org/10.6314/JIMT.202008_31(4).07

摘要

台灣第二型糖尿病的發生率和盛行率逐年提高，顯示了控制糖尿病及其併發症是相當重要的課題。糖尿病的治療主要來自於生活型態的調整和藥物使用，其中二甲雙胍類口服降血糖藥metformin是美國及中華民國糖尿病醫學會皆建議第一線使用的藥物。Metformin有不易低血糖、不增加體重、及改善心血管併發症等優點，但仍需注意有些人可能會產生腸胃道症狀、乳酸中毒、維生素B12缺乏等副作用。維生素B12參與了DNA和RNA的合成及造血，並影響神經元作用，若是缺乏可能會產生血液學方面的變化像是貧血、或神經學症狀，例如：周邊神經病變、認知功能下降。維生素B12缺乏的機轉可能源自於metformin干擾了腸胃道吸收維生素B12的過程，有許多研究顯示使用metformin的病人，血中維生素B12的濃度比起未使用者相對較低，而其他相關的檢驗，如：methylmalonic acid和homocysteine以及神經學的檢查也有差異。由於維生素B12在生理上扮演了相當重要的角色，因此對於長期使用metformin的病人應謹慎觀察是否有B12缺乏的相關症狀，並考慮規則追蹤血液和神經學檢查，若是發現B12缺乏，除了要鑑別診斷排除其他可能的病因外，治療上需長期補充維生素B12。

關鍵字

糖尿病（Diabetes mellitus） ； 二甲雙胍（Metformin） ； 維生素B12（Vitamin B12） ； 鈷胺素（Cobalamin）

並列摘要

In Taiwan, the incidence and prevalence of type 2 diabetes mellitus have increased year by year, suggesting the issue of controlling diabetes and its complications cannot be ignored. The treatments of diabetes include lifestyle modification and medication use. Current guideline from American Diabetes Association and Diabetes Association of the Republic of China (Taiwan) recommend dimethylbiguanide, also known as metformin, as first-line therapy for patients with type 2 diabetes concurrent with lifestyle intervention. Metformin has beneficial effects on glycemic control and preventing cardiovascular complications. Furthermore, it has no risk of hypoglycemia and weight gain. Despite these advantages, it is worth to note that some patients may have side effect such as gastrointestinal discomfort, rarely lactic acidosis, and potential for vitamin B12 deficiency. Vitamin B12 plays a role in DNA and RNA synthesis, hematopoiesis, and neuronal function; if it is lacking, hematological changes like anemia and neurological manifestation including peripheral neuropathy and cognitive decline may develop. The mechanism of metformin-induced B12 deficiency may result from interference of metformin in the absorption of vitamin B12 in the ileum. Many studies have demonstrated lower concentration of serum vitamin B12, higher concentration of serum methylmalonic acid and homocysteine, and more neuropathy in patients using metformin than non-users. Because vitamin B12 is important to physiology, regular screening for B12 deficiency and related symptoms is recommended for patients with long-term use of high-dose metformin. Once vitamin B12 deficiency is confirmed, excluding possible etiology other than metformin, persistent vitamin B12 supplement is required.