二甲雙胍的臨床地位與使用時機，一文教你get!丨專家共識解讀第一篇

耘禾 2019-07-17

展開全文

手把手教你正確掌握二甲雙胍的臨床地位與使用時機。

糖尿病患者心血管事件發(fā)生風險顯著增高，長期以來受到內分泌、心血管領域醫(yī)師廣泛關注。作為一種臨床應用已有60多年歷史的降糖藥，二甲雙胍已成為全球糖尿病防控的核心藥物。因此，正確認識、合理使用二甲雙胍對心血管醫(yī)師來說同樣至關重要。

近期，《二甲雙胍臨床應用專家共識》（下文簡稱“共識”）?2018版正式公布。基于近年來不斷涌現的二甲雙胍相關研究新證據，共識做出部分更新與修訂，為廣大臨床醫(yī)師提供重要的學術參考。我們將依據專家共識，對每部分內容進行具體解讀，今天先跟小編一起來了解“二甲雙胍的臨床地位與使用時機”。

表：二甲雙胍的臨床地位與使用時機

T2DM治療的一線首選和全程用藥，

二甲雙胍當仁不讓！

共識推薦，如無禁忌癥和不耐受，二甲雙胍是治療T2DM的首選全程用藥，且應一直保留在糖尿病治療方案中。那么，二甲雙胍為何能夠在眾多降糖藥中脫穎而出，讓共識為它打Call呢？

首先，二甲雙胍兼具短期和長期降糖療效，單獨使用可有效降低T2DM患者的空腹血糖（FPG）和餐后血糖（PPG）。研究表明二甲雙胍可使中國新診斷T2DM患者的HbA_1c降低1.8%，且不受體重影響^?^[1]。基線HbA_1c水平一致時，最佳有效劑量（2000 mg/d）的二甲雙胍降糖療效優(yōu)于其他口服降糖藥^?^[2]。二甲雙胍緩釋片與普通片的療效相似。

其次，二甲雙胍單藥治療效果不佳者，聯(lián)合其他口服降糖藥可進一步獲得明顯的血糖改善。與使用其他口服降糖藥作為一線治療相比，以二甲雙胍作為一線治療的患者，加用第二種口服降糖藥或啟動胰島素聯(lián)合治療的開始最晚，后續(xù)需要調整治療方案的概率也最低^{[3, 4]}。二甲雙胍聯(lián)合胰島素可進一步降低HbA_1c、減少胰島素用量、增加體重并降低低血糖風險^[5-8]。

再次，二甲雙胍具有心血管保護作用。二甲雙胍的長期治療與新診斷的T2DM患者、已存在心血管疾病的T2DM患者的心血管事件發(fā)生風險降低顯著相關^[9]。此外，薈萃分析顯示，二甲雙胍可降低糖尿病患者的全因死亡率^{[9, 10]}。

最后，二甲雙胍良好的安全性和耐受性是其長期應用的保障。單獨使用時不增加低血糖發(fā)生的風險，胃腸道反應多為一過性、不導致腎臟損害，長期使用不增加高乳酸血癥或乳酸酸中毒發(fā)生風險^?^[11-13]。與其他降糖藥物相比，二甲雙胍具有良好的成本-效益比。

不超重、不肥胖的T2DM患者，

也應該首選二甲雙胍！

回顧性和前瞻性臨床研究結果均顯示，二甲雙胍在肥胖、超重、正常體重的T2DM患者中療效相當。因此，體重不是能否使用二甲雙胍治療的決定因素，無論對于超重、肥胖或體重正常的患者，國內外主要糖尿病指南均將二甲雙胍推薦為治療T2DM的首選用藥?^[^{14, 15]}。

防范糖尿病于未然，二甲雙胍也有功！

值得一提的是，除治療效果成績斐然外，大量證據尚顯示二甲雙胍可以有效且安全地降低糖尿病前期人群發(fā)展為T2DM的發(fā)生率^?[16]、減少患者體重增加且10年內醫(yī)療花費更低?^{[17, 18]}，但我國尚未批準二甲雙胍應用于糖尿病的預防。

鑒于大量研究證據表明二甲雙胍具有確切的降糖效果和包括改善心血管結局在內的多重優(yōu)勢，專家共識仍然力薦二甲雙胍作為首選和全程用藥奮戰(zhàn)于T2DM治療一線。

下期預告：

二甲雙胍的作用機制

參考文獻：

[1]Ji L, Li H, Guo X, et al. Impact of baseline BMI on glycemic control and weight change with metformin monotherapy in Chinese type 2 diabetes patients: phase IV open-label trial. PloS one. 2013; 2: e57222.

[2]Esposito K, Chiodini P, Bellastella G, et al. Proportion of patients at HbA1c target <7% with="" eight="" classes="" of="" antidiabetic="" drugs="" in="" type="" 2="" diabetes:="" systematic="" review="" of="" 218="" randomized="" controlled="" trials="" with="" 78="" 945="" patients.="" diabetes,="" obesity="" &="" metabolism.="" 2012;="" 3:="">

[3]Berkowitz SA, Krumme AA, Avorn J, et al. Initial choice of oral glucose-lowering medication for diabetes mellitus: a patient-centered comparative effectiveness study. JAMA internal medicine. 2014; 12: 1955-62.

[4]Ji L, Lu J, Weng J, et al. China type 2 diabetes treatment status survey of treatment pattern of oral drugs users. Journal of diabetes. 2015; 2: 166-73.

[5]Hemmingsen B, Christensen LL, Wetterslev J, et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. Bmj. 2012: e1771.

[6]Strowig SM, Aviles-Santa ML, Raskin P. Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and troglitazone in type 2 diabetes. Diabetes care. 2002; 10: 1691-8.

[7]Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Archives of internal medicine. 2009; 6: 616-25.

[8]Guo L, Chen L, Chang B, et al. A randomized, open-label, multicentre, parallel-controlled study comparing the efficacy and safety of biphasic insulin aspart 30 plus metformin with biphasic insulin aspart 30 monotherapy for type 2 diabetes patients inadequately controlled with oral antidiabetic drugs: The merit study. Diabetes, obesity & metabolism. 2018; 12: 2740-2747.

[9]Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. The New England journal of medicine. 2008; 15: 1577-89.

[10]Campbell JM, Bellman SM, Stephenson MD, et al. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. Ageing research reviews. 2017: 31-44.

[11]Wright AD, Cull CA, Macleod KM, et al. Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73. Journal of diabetes and its complications. 2006; 6: 395-401.

[12]Rachmani R, Slavachevski I, Levi Z, et al. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. European journal of internal medicine. 2002; 7: 428.

[13]Cryer DR, Nicholas SP, Henry DH, et al. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes care. 2005; 3: 539-43.

[14]Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by the American Association Of Clinical Endocrinologists And American College Of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm - 2018 Executive Summary. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2018; 1: 91-120.

[15]Introduction: Standards of Medical Care in Diabetes-2018. Diabetes care. 2018; Suppl 1: S1-S2.

[16]Li CL, Pan CY, Lu JM, et al. Effect of metformin on patients with impaired glucose tolerance. Diabetic medicine : a journal of the British Diabetic Association. 1999; 6: 477-81.

[17]Diabetes Prevention Program Research G. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes care. 2012; 4: 723-30.

[18]Diabetes Prevention Program Research G. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes care. 2012; 4: 731-7.