Diabetes Metab J.  2020 Feb;44(1):3-10. 10.4093/dmj.2020.0004.

Metformin Treatment for Patients with Diabetes and Chronic Kidney Disease: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement

• Hur KY
• Kim MK
• Ko SH
• Han M
• Lee DW
• Kwon HS
• Committee of Clinical Practice Guidelines, Korean Diabetes Association
• Committee of the Cooperative Studies, Korean Society of Nephrology

• KMID: 2470951
• DOI: http://doi.org/10.4093/dmj.2020.0004

Abstract

The safety of metformin use for patients with type 2 diabetes mellitus (T2DM) and advanced kidney disease is controversial, and more recent guidelines have suggested that metformin be used cautiously in this group until more definitive evidence concerning its safety is available. The Korean Diabetes Association and the Korean Society of Nephrology have agreed on consensus statements concerning metformin use for patients with T2DM and renal dysfunction, particularly when these patients undergo imaging studies using iodinated contrast media (ICM). Metformin can be used safely when the estimated glomerular filtration rate (eGFR) is ≥45 mL/min/1.73 m². If the eGFR is between 30 and 44 mL/min/1.73 m², metformin treatment should not be started. If metformin is already in use, a daily dose of ≤1,000 mg is recommended. Metformin is contraindicated when the eGFR is <30 mL/min/1.73 m². Renal function should be evaluated prior to any ICM-related procedures. During procedures involving intravenous administration of ICM, metformin should be discontinued starting the day of the procedures and up to 48 hours post-procedures if the eGFR is <60 mL/min/1.73 m².

Keyword

Contrast media; Diabetes mellitus; Metformin; Renal insufficiency

MeSH Terms

Administration, Intravenous
Consensus*
Contrast Media
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glomerular Filtration Rate
Humans
Kidney Diseases
Metformin*
Nephrology*
Renal Insufficiency
Renal Insufficiency, Chronic*
Contrast Media
Metformin

Figure

• 

  Fig. 1 Secular trends in antidiabetic medication prescriptions in adults with type 2 diabetes mellitus, according to kidney function: (A) in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, (B) in patients with eGFR between 45 and 59 mL/min/1.73 m2, and (C) in patients with an eGFR between 30 and 44 mL/min/1.73 m2. SU, sulfonylurea; MFOM, metformin; GLN, glinide; TZD, thiazolidinedione; DPP-4i, dipeptidyl peptidase-4 inhibitor; α-Gi, α-glucosidase inhibitor.

Reference

1. Kim KS, Park SW, Cho YW, Kim SK. Higher prevalence and progression rate of chronic kidney disease in elderly patients with type 2 diabetes mellitus. Diabetes Metab J. 2018; 42:224–232.

2. Bae JC. Trends of diabetes epidemic in Korea. Diabetes Metab J. 2018; 42:377–379.

3. Kim KJ, Kwon TY, Yu S, Seo JA, Kim NH, Choi KM, Baik SH, Choi DS, Kim SG, Park Y, Kim NH. Ten-year mortality trends for adults with and without diabetes mellitus in South Korea, 2003 to 2013. Diabetes Metab J. 2018; 42:394–401.

4. Kim BY, Won JC, Lee JH, Kim HS, Park JH, Ha KH, Won KC, Kim DJ, Park KS. Diabetes fact sheets in Korea, 2018: an appraisal of current status. Diabetes Metab J. 2019; 43:487–494.

5. Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, Kurella Tamura M, Feldman HI. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014; 63:713–735.

6. Clemens KK, Liu K, Shariff S, Schernthaner G, Tangri N, Garg AX. Secular trends in antihyperglycaemic medication prescriptions in older adults with diabetes and chronic kidney disease: 2004-2013. Diabetes Obes Metab. 2016; 18:607–614.

7. Hung SC, Chang YK, Liu JS, Kuo KL, Chen YH, Hsu CC, Tarng DC. Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study. Lancet Diabetes Endocrinol. 2015; 3:605–614.

8. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42:Suppl 1. S90–S102.

9. U.S. Food and Drug Administration: FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. cited 2020 Jan 28. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm.

10. Packer M. Is metformin beneficial for heart failure in patients with type 2 diabetes? Diabetes Res Clin Pract. 2018; 136:168–170.

11. Aharaz A, Pottegard A, Henriksen DP, Hallas J, Beck-Nielsen H, Lassen AT. Risk of lactic acidosis in type 2 diabetes patients using metformin: a case control study. PLoS One. 2018; 13:e0196122.

12. Lee EY, Hwang S, Lee YH, Lee SH, Lee YM, Kang HP, Han E, Lee W, Lee BW, Kang ES, Cha BS, Lee HC. Association between metformin use and risk of lactic acidosis or elevated lactate concentration in type 2 diabetes. Yonsei Med J. 2017; 58:312–318.

13. Tseng CH. Metformin use is associated with a lower risk of hospitalization for heart failure in patients with type 2 diabetes mellitus: a retrospective cohort analysis. J Am Heart Assoc. 2019; 8:e011640.

14. Chan NN, Brain HP, Feher MD. Metformin-associated lactic acidosis: a rare or very rare clinical entity? Diabet Med. 1999; 16:273–281.

15. Oates NS, Shah RR, Idle JR, Smith RL. Influence of oxidation polymorphism on phenformin kinetics and dynamics. Clin Pharmacol Ther. 1983; 34:827–834.

16. Richy FF, Sabido-Espin M, Guedes S, Corvino FA, Gottwald-Hostalek U. 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; 37:2291–2295.

17. Luft D, Schmulling RM, Eggstein M. Lactic acidosis in biguanide-treated diabetics: a review of 330 cases. Diabetologia. 1978; 14:75–87.

18. Lalau JD. Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf. 2010; 33:727–740.

19. Lalau JD, Kajbaf F, Protti A, Christensen MM, De Broe ME, Wiernsperger N. Metformin-associated lactic acidosis (MALA): moving towards a new paradigm. Diabetes Obes Metab. 2017; 19:1502–1512.

20. European Medicines Agency: Note for guidance on the evaluation of the pharmacokinetics of medicinal products in patients with impaired renal function. cited 2020 Jan 28. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003123.pdf.

21. Lalau JD, Kajbaf F, Bennis Y, Hurtel-Lemaire AS, Belpaire F, De Broe ME. Metformin treatment in patients with type 2 diabetes and chronic kidney disease stages 3A, 3B, or 4. Diabetes Care. 2018; 41:547–553.

22. Kim MK, Ko SH, Kim BY, Kang ES, Noh J, Kim SK, Park SO, Hur KY, Chon S, Moon MK, Kim NH, Kim SY, Rhee SY, Lee KW, Kim JH, Rhee EJ, Chun S, Yu SH, Kim DJ, Kwon HS, Park KS. Committee of Clinical Practice Guidelines, Korean Diabetes Association. 2019 Clinical practice guidelines for type 2 diabetes mellitus in Korea. Diabetes Metab J. 2019; 43:398–406.

23. Herts BR, Schneider E, Poggio ED, Obuchowski NA, Baker ME. Identifying outpatients with renal insufficiency before contrast-enhanced CT by using estimated glomerular filtration rates versus serum creatinine levels. Radiology. 2008; 248:106–113.

24. Davenport MS, Khalatbari S, Cohan RH, Ellis JH. Contrast medium-induced nephrotoxicity risk assessment in adult inpatients: a comparison of serum creatinine level- and estimated glomerular filtration rate-based screening methods. Radiology. 2013; 269:92–100.

25. Choyke PL, Cady J, DePollar SL, Austin H. Determination of serum creatinine prior to iodinated contrast media: is it necessary in all patients? Tech Urol. 1998; 4:65–69.

26. Tippins RB, Torres WE, Baumgartner BR, Baumgarten DA. Are screening serum creatinine levels necessary prior to outpatient CT examinations? Radiology. 2000; 216:481–484.

27. Baumgarten DA, Ellis JH. Contrast-induced nephropathy: contrast material not required. AJR Am J Roentgenol. 2008; 191:383–386.

28. Davenport MS, Cohan RH, Khalatbari S, Ellis JH. The challenges in assessing contrast-induced nephropathy: where are we now? AJR Am J Roentgenol. 2014; 202:784–789.

29. Ellis JH, Cohan RH. Reducing the risk of contrast-induced nephropathy: a perspective on the controversies. AJR Am J Roentgenol. 2009; 192:1544–1549.

30. Katzberg RW, Newhouse JH. Intravenous contrast medium-induced nephrotoxicity: is the medical risk really as great as we have come to believe? Radiology. 2010; 256:21–28.

31. McDonald JS, McDonald RJ, Carter RE, Katzberg RW, Kallmes DF, Williamson EE. Risk of intravenous contrast material-mediated acute kidney injury: a propensity score-matched study stratified by baseline-estimated glomerular filtration rate. Radiology. 2014; 271:65–73.

32. Newhouse JH, RoyChoudhury A. Quantitating contrast medium-induced nephropathy: controlling the controls. Radiology. 2013; 267:4–8.

33. Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B, Uder M. Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology. 2005; 235:843–849.

34. Sendeski M, Patzak A, Pallone TL, Cao C, Persson AE, Persson PB. Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy. Radiology. 2009; 251:697–704.

35. Haight AE, Kaste SC, Goloubeva OG, Xiong XP, Bowman LC. Nephrotoxicity of iopamidol in pediatric, adolescent, and young adult patients who have undergone allogeneic bone marrow transplantation. Radiology. 2003; 226:399–404.

36. Senthilnathan S, Gauvreau K, Marshall AC, Lock JE, Bergersen L. Contrast administration in pediatric cardiac catheterization: dose and adverse events. Catheter Cardiovasc Interv. 2009; 73:814–820.

37. Korean Institute of Drug Safety & Risk Management: Drug safety information report trend (2018). updated 2019 Mar 4. Available from: open.drugsafe.or.kr/trend/trend/Read.jsp?ntt_id=2124.

38. Shah AD, McHargue C, Yee J, Rushakoff RJ. Intravenous contrast in patients with diabetes on metformin: new common sense guidelines. Endocr Pract. 2016; 22:502–505.

39. Goergen SK, Rumbold G, Compton G, Harris C. Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology. 2010; 254:261–269.

40. ACR Committee on Drugs and Contrast Media: ACR manual on contrast media. Version 10.3. 2018. updated 2017 May 31. Available from: https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf.

41. European Society of Urogenital Radiology: ESUR guidelines on contrast agents. Version 10.0. cited 2020 Jan 28. Available from: http://www.esur.org/fileadmin/content/2019/ESUR_Guidelines_10.0_Final_Version.pdf.

42. Han S, Yoon SH, Lee W, Choi YH, Kang DY, Kang HR. Management of adverse reactions to iodinated contrast media for computed tomography in Korean referral hospitals: a survey investigation. Korean J Radiol. 2019; 20:148–157.

43. Corremans R, Vervaet BA, D'Haese PC, Neven E, Verhulst A. Metformin: a candidate drug for renal diseases. Int J Mol Sci. 2018; 20:E42.

44. Korea Ministry of Food and Drug Safety: Instructions on the change of permit for metformin hydrochloride (tablet) (uniform adjustment). updated 2018 Jan 3. Available from: https://nedrug.mfds.go.kr/bbs/58/2683/.