Sparkes Steven T, Patel Dhiren K, Goldman-Levine Jennifer D
Harvard University Health Services Pharmacy, Cambridge, MA, USA.
MCPHS University, Boston, MA, USA.
J Pharm Technol. 2014 Dec;30(6):227-234. doi: 10.1177/8755122514544527. Epub 2014 Jul 24.
To review why metformin is considered first-line therapy for type 2 diabetes mellitus (T2DM) and review newer avenues of research currently being evaluated. The Cochrane Library and Medline (to January 2014) were searched for case-control and cohort studies, clinical trials, and systematic reviews and meta-analyses involving metformin for any indication. The literature search found 5 major avenues of research for metformin: reduction in mortality, delayed-onset or prevention of T2DM in the presence of prediabetes, nonalcoholic fatty liver disease (NAFLD), polycystic ovarian syndrome (PCOS), and decreased cancer risk. When available, multi-center, double-blind, controlled clinical trials or meta-analyses thereof were selected for review. If these types of studies did not exist, other types of studies were chosen for review. Metformin significantly decreases all-cause and diabetes-related mortality in overweight and obese patients with T2DM. It may also decrease risk of progression to T2DM in patients with prediabetes. Metformin has been studied for the treatment of NAFLD though data are limited. Metformin alone or combined with clomiphene may increase pregnancy and ovulation rates but has not yet been shown to increase live-birth rates in patients with PCOS. Metformin may decrease risk of colorectal cancer but not all-cancer risk. Metformin's clinical role in T2DM and prediabetes is well established. Other avenues of research being evaluated at this time are NAFLD, PCOS, and reduced risk of cancer; more data are needed before it has a clinical role in these indications.
回顾二甲双胍被视为2型糖尿病（T2DM）一线治疗药物的原因，并审视目前正在评估的新研究方向。检索考克兰图书馆和Medline（截至2014年1月），查找涉及二甲双胍任何适应证的病例对照研究、队列研究、临床试验以及系统评价和荟萃分析。文献检索发现二甲双胍有5个主要研究方向：降低死亡率、在存在糖尿病前期时延迟发病或预防T2DM、非酒精性脂肪性肝病（NAFLD）、多囊卵巢综合征（PCOS）以及降低癌症风险。如有多中心、双盲、对照临床试验或其荟萃分析，将其选入进行综述。若不存在这类研究，则选择其他类型的研究进行综述。二甲双胍可显著降低超重和肥胖T2DM患者的全因死亡率和糖尿病相关死亡率。它还可能降低糖尿病前期患者进展为T2DM的风险。虽然数据有限，但已对二甲双胍治疗NAFLD进行了研究。二甲双胍单独使用或与克罗米芬联合使用可能会提高PCOS患者的妊娠率和排卵率，但尚未证明能提高活产率。二甲双胍可能降低结直肠癌风险，但不能降低所有癌症的风险。二甲双胍在T2DM和糖尿病前期的临床作用已得到充分确立。目前正在评估的其他研究方向包括NAFLD、PCOS和降低癌症风险；在其在这些适应证中发挥临床作用之前，还需要更多数据。
