Metformin and Lactic Acidosis in Diabetic Patients
Metformin is the basic drug in the clinical treatment of Diabetes, often used in the treatment of Type 2 Diabetes Mellitus (T2DM).Its effect has been fully verified in the clinical treatment of T2DM. However, in the treatment of T2DM with metformin, there is still a certain probability of related lactic acidosis, and the fatality rate is high. Therefore, is the use of metformin drug treatment a direct risk factor for lactic acidosis in diabetic patients? This paper will review the hypoglycemic mechanism of metformin and related studies on lactic acidosis, so as to further explore the relationship between metformin and lactic acidosis in diabetic patients, and provide help and reference for metformin drugs in the clinical treatment of T2DM.
Keywords:Metformin, T2DM, Lactate acidosis
 American Diabetes Association.Standards of medical care in diabetes-2011［J］.Diabetes Care，011，34( 5) : 11-60．
 Nathan DM,Buse JB,Davidson MB,et al.Medical management of hyperglycaemia in type 2 diabetes mellitus: A consensus algorithm for the initiation and adjnstment of therapy: a consensus statement from the American diabetes association and the European Association for the study of diabetes [J]．Diabetolgia, 2009, 52(1) : 17 -30.
 Yang WY. Guidelines for the prevention and treatment of type 2 diabetes in China [M]. Beijing:Peking University Medical Press, 2010:21.
 Almirall J, Briculle M, Gonzalez clemente JM.Metformin-as-sociated lactic acidosis in type 2 diabetes mellitus : incidence and presentation in common elinical practice. Nephrol Dial Trans-plant[J],2008,23:2436- 2438.
 Xianbin Cai,Xi Hu,Bozhi Cai,et al. Metformin suppresses hepatocellular carcinoma cell growth through inductionof cell cycle G1/G0 phase arrest and p21CIP and p27KIP expression and downregulationof cyclin D1 in vitro and in vivo[J]. Oncology Reports,2013,30(5).
 KlarenbachS,CameronC,SinghS,etal.Cost-effectiveness of second-line anti -hyperglycemictherapy in patients with type 2 diabetes mellitusinade quately controlled on metformin [J].CanMedAssoc J,2011,183(16):E1213-1220.
 Yang K. Study on the mechanism of sea-buckthorn seed flavonoids promoting glucose uptake in fat and skeletal muscle cells [D]. East China Normal University, 2017.
 Hur KY,Lee MS.Gutmicrobiota and metabolic disorders Diabetes MetabJ[J],2015,39;198-203.
 Everard A, Lazarevic V, Gaia N, Johansson M,Stahlman M, Backhed F, Delzenne NM, Schrenzel J,Francois P, Cani PD. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity[J]. ISME J, 2014;8:2116–2130.
 de Kort S, Keszthelyi D, Masclee AA. Leaky gut and diabetes mellitus: what is the link?[J], Obes Rev 2011;12:449–458.
 Mu Yiming, Ji Linong, Li Chunlin, et al. Expert consensus on the clinical application of metformin (2018 edition). Chinese Journal of Diabetes,2019, 27 (3):161-173.
 Maida A,Lamont BJ,Cao X,et al.Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice.Diabetologia,2011,54(2):339-349.
 Cho YM,Kieffer TJ. New aspects of an old drug:metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser[J]. Diabetologia,2011,54(2):219-222.
 Viollet B,Guigas B,Sanz Garcia N,et al.Celluar and molecular mechanisms of metforminan overview.Clinical Science,2012,122:253-270.
 Caton PW,Nayuni NK,Kieswich J,et al.Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5.J Endocrinol,205:97-106.
 Foretz M,Hebrard S,Leclerc J,et al.Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state[J]. The Journal of Clinical Investigation,2010,120(7):2355-2369.
 Miller Russell A,Chu Q,Xie J,et al.Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP[J]. Nature,2013,494(7436).
 Carolina Gutiérrez-Repiso,Isabel Moreno-Indias,et al.Mucosa-associated microbiota in the jejunum of patients with morbid obesity: alterations in states of insulin resistance and metformin treatment[J]. Surgery for Obesity and Related Diseases,2020:1878-7533.
 Qingling Meng, Xiuping Jin, Naijun Wu, Weibo Yang. Effects of metformin on the expression of adenylate activated protein kinase and glucose transporter 4 in insulin-resistant mouse embryonic fibroblasts [J]. Chinese Journal of Diabetes,2014,22(02):177-180.
 Wang Zhanjian, Tan Lixin. Metformin improves insulin resistance [J]. Drug Evaluation,2010,7(13):17.
 Hu Baoji, Bo Lulong, Deng Xiaoming, Duan Hongwei. Chinese Journal of Medical Review,2018,15(03):22-25.
 Kajbaf F，Lalau JD．The criteria for metformin-associated lactic acidosis: the quality of reporting in a large pharmacovigilance da-tabase[J]．Diabetic Med, 2013, 30( 3) : 345-348．
 Lu ZQ. The value of metguanidine hypoglycemic drugs in the treatment of type 2 diabetes mellitus [J].Journal of Clinical Therapeutics,2010,8(04):33-38.
 Inzucchi,SE,BergenstalRM,Buse JB,et al.Management of hyperglycemia in type2 diabetes,2015:A patient-centered approach:Update to a position statement of the American Diabetes Association and the European Association for the study of diabetes[J].Diabetes Care, 2015,38:140-149.
 McAlister FA, Majumdar SR, Eurich DT et al.The effect of specialist care within the first year on subsequent outcomes in 24 232 adults with new-onset diabetes mellitus: popula- tion-based cohort study.Qual Saf Health Care, 2007, 16(1) : 6 -11．
 Salpeter S, Ureyber E, Pasternak U, et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus[J]. Cochrane Database Syst Rev, 2010,4: CD002967.
 Inzucchi SE，Lipska KJ，Mayo H，et al． Metformin in patients with type 2 diabetes and kidney disease a systematic review.JA- MA,2014，312( 24): 2668-2675．
 Richy FF, Sabido-Espin M, Guedes S, et al. Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study．Diabetes Care, 2014, 37(8) : 2291-2295．
 Aharaz A, Pottegard A, Henriksen DP, et al. Risk of lactic aci- dosis in type 2 diabetes patients using metformin: A case control study. PloS One，2018, 13(5) : e0196122．
 Scale T, Harvey JN.Diabetes,Metformin and lactic acidosis [J]. Clin Endocrinol (Oxf), 2011,74( 2) :191-196．
 Nathan DM ,EuseIB ,Davidzcn MS, et al.Medicai management of hyperglycaemia in type 2 diabetes mellitus; Acon-sensus algorithm for the initiation and adinsmen of therapy:a consensus statement from the American diabeies asseciation and the European Association for the study of diabeteg[J]. Diabetolgia,2009,52(1);17-30.
 Tian Hui, Li Chunlin, Yang Guang, et al. Safety evaluation of metformin in elderly patients with type 2 diabetes mellitus. Chinese Journal of Internal Medicine, 2008,47:914-918.
 Wang Xiaobing, Ye Shandong. Research progress of metformin related lactic acidosis [J]. Anhui Medical Journal,2014,35(01):130-133.
 Deng Shiman.Study on the correlation between hemoglobin A1c, serum lactic acid level and cardiac dysfunction [J]. China Contemporary Medicine,2019,26(1): 45-47.
 Chen Haiyan, Wang Yinghuo. Clinical significance and prognosis evaluation of serum lactic acid monitoring in patients with cardiogenic shock [J]. Chinese Journal of Traditional Medicine,2020(03):92-95.
 Andersson C，Olesen JB，Hansen P Ｒ，et al.Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort stud［J］．Diabetologia，2010，53 ( 12) : 2546 -2553．
 Evans JM，Doney AS，AlZadjali MA，et al．Effect of Metform in on mortality in patients with heart failure and type 2 diabetes mellitus［J］．Am J Cardiol，2010，106 (7): 1006-1010．
 Roussel R, Travert F，Pasquet B，et al． Reduction of Atherothrombosis for Continued Health (REACH)Registry Investigators. Metformin use and mortality among patients with diabetes and atherothrombosis[J]. Arch Intern Med, 2010, 170 ( 21) : 1892-1899.
 lalau JD,Race J.Lactic acidosis inmetfoxmin-txeaied pa-tients. RPrognosiic value of axiexial lsciate levels and plasmameifoxmis concentrations[J].Drug Sef ,1999 ,20(4):.371-384.
 Krzymień J, Karnafel W. Lactic acidosis in patients with diabetes[J].Pol Arch Med Wewn, 2013,123(3):91 -97.
 McAlister FA, Majumdar SR, Eurich DT, et al. The effect of specialist care within the first year on subsequent outcomesin 24 232 adults with new-onset diabetes mellitus: popula-tion-based cohort study [J]Qual Saf Health Care, 2007, 16( 1) : 6-11．
 Yu Huazhong, Li Zhangping, Wu Chaoming,Cheng Junyan, Chen Shouquan. Analysis of the characteristics of lactic acidosis in diabetic patients taking metformin [J]. Journal of Practical Medicine,2006(07):804-805.
 Lin YC, Lin LY, Wang HF, Lin HD. Fasting plasma lactate concentrations in ambulatory elderly patients with type 2 dia- betes receiving metformin therapy:a retrospective cross-sec- tional study[J].Chin Med Assoc, 2010, 73 (12) : 617-622.
 Salpeter SR ,Greyber E, Pasternak GA.et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev, 2010, 4:CD002967.
 Cryer DR. Nicholas SP, Henry DH.et al. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes Care, 2005 ,28:539-543.