二甲雙胍類降血糖藥物「Metformin」：過去、現在與未來

Metformin: The Past, Present, and Future

林建良(Jiann-Liang Lin) ； 許惠恒(Wayne Huey-Herng Sheu) ； 沈宜靜(Yi-Jing Sheen)

《內科學誌》 24卷6期 (2013/12) Pp. 477-486

https://doi.org/10.6314/JIMT.2013.24(6).06

摘要

根據流行病學資料，全球第二型糖尿病盛行率逐年上升，口服降血糖藥的發展也隨需求增加不斷精進。除了新藥的開發，現行藥物的新展望也是重要研究方向。二甲雙胍類降血糖藥物「metformin」是歷史悠久，目前使用最廣泛，且在歐美相關糖尿病醫學會都建議治療第二型糖尿病優先選擇的口服降血糖藥。此藥不增加體重，單獨使用低血糖風險低，並有研究報告提出其在糖尿病併發症與相關疾病，如糖尿病心血管併發症、多囊卵巢候群等的益處。此外，近來流行病學、臨床觀察與體內、體外研究有初步證據顯示metformin對於某些惡性腫瘤發生與預後有幫助。目前文獻提到使用metformin有益的惡性腫瘤包括：肝癌、胰臟癌、大腸直腸癌、乳癌、前列腺癌、肺癌以及卵巢癌，可能透過一些直接（非關胰島素增敏）與間接（胰島素增敏相關）的機轉。未來需更多大型前瞻性研究以確立其獨立於改善胰島素抗性與減重之外的直接抗癌臨床應用效益。至於metfomin在其他可能減少糖尿病相關腎小管損傷、改善糖尿病患肝性腦病變、改善高血糖相關免疫抑制、治療失智與抗老等議題的角色，仍存有許多未知與疑議，有待相關釐清與進一步的臨床證據。因此，第二型糖尿病患者在沒有禁忌症的情形下，二甲雙胍類藥物metformin是治療第二型糖尿病的首選用藥。

關鍵字

第二型糖尿病（Type 2 diabetes mellitus） ； 二甲雙胍類藥物（Dimethylbiguanide-metformin）

並列摘要

In facing the alarming increased prevalence of type 2 diabetes worldwide, a large number of researches aimed to develop ideal anti-diabetic drugs as well as explore the further advantages of current used medications. Currently, dimethylbiguanide or metformin is the most widely prescribed agent for treating diabetes. Furthermore, recent guidelines from the American Diabetes Association, European Association of the Study of Diabetes, and American Association of Clinical Endocrinologists recommend metformin as first-line oral therapy for patients with diabetes. Use of metformin does not lead to weight gain, and it rarely causes hypoglycemia. Previous studies have reported the beneficial effects of metformin in the complications of type 2 diabetes, such as cardiovascular disease and polycystic ovary syndrome. Recent studies also revealed that use with metformin might associate with reduced incidence and mortality in several cancers including colorectal, pancreatic, hepatocellular, breast, ovarian, prostate, and lung cancer. Resutls from in vivo and in vitro studies have shown that metformin exerts its anti-cancer effects through direct (insulin-independent) and/or indirect (insulin-dependent) mechanisms. Large-scale prospective studies to elaborate the relationships among diabetes, cancer, and gender are thus warranted. Additionally, further studies may contribute to its wider use in certain degree of nephropathy, hepatic encephalopathy, Alzheimer's disease, as well as for improving the immunosuppressive and anti-aging effects. It is suggested that metformin be used as first-line therapy for type 2 diabetic patients without contraindications, in addition to lifestyle interventions.