Abstract
Current therapy directed at delaying the progression of diabetic renal disease includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is not complete. There is a scarcity of studies analyzingthe nephroprotective effect of antihyperglycemicdrugs beyond their glucose lowering effect and progression of diabetic renal disease. This article updatethe existing data about metformin in diabetic kidney diseaseReferences
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2. Anand S., Bitton A., Gaziano T. The gap between estimated incidence of end-stage renal disease and use of therapy. PLoS ONE. 2013;8:e72860. Disponible en: https://doi.org/10.1371/journal.pone.0072860
3. Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME. Diabetic kidney disease: a report from an ADA Consensus Conference. Am J Kidney Dis. 2014;64(4):510-33. Disponible en: https://doi.org/10.1053j.ajkd.2014.08.001
4. National Kidney Foundation. KDOQI Clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60(5):850-86. Disponible en: https://doi.org/10.1053/j.ajkd.2012.07.005
5. Lopez-Giacoman S, Madero M. Biomarkers in chronic kidney disease, from kidney function to kidney damage. World J Nephrol. 2015;4(1):57-73. Disponible en: https://doi.org/10.5527/wjn.v4.i1.57
6. Adler AI, Stevens RJ, Manley SE, et al. Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63:225-32. Disponible en: https://doi.org/10.1046/j.1523-1755.2003.00712.x
7. Mora-Fernández C, Domínguez-Pimentel V, de Fuentes MM, Górriz JL, Martínez-Castelao A, Navarro-González JF. Diabetic kidney disease: from physiology to therapeutics. J Physiol. 2014;592(18):3997-4012. Disponible en: https://doi.org/10.1113/jphysiol.2014.272328
8. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 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. Diabetes Care. 2015;38(1):140-9. Disponible en: https://doi.org/10.2337/dc14-2441
9. American Diabetes Association. Pharmacological approaches to glycemic treatment. Diabetes Care, 2017;40(Suppl. 1):S64-74. Disponible en: https://doi.org/10.2337/dc17-S012
10. Anabtawi A, Miles JM. Metformin: Nonglycemic effects and potential novel indications. Endocr Pract. 2016;22(8):999-1007. Disponible en: https://doi.org/10.4158/EP151145.RA
11. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854-65. Disponible en: https://doi.org/10.1016/S0140-6736(98)07037-8
12. US 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. April 8, 2016. Disponible en: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM494140.pdf Accedido: Octubre 12, 2016.
13. European Medicines Agency. Use of metformin to treat diabetes now expanded to patients with moderately reduced kidney function. 14 October 2016. EMA/603690/2016. Disponible en:www.ema.europa.eu/.../index.jsp?curl=pages/news_and_events/news/201610/news_detail_002620.jsp&mid=WC - 45k Accedido: Noviembre 15, 2016.
14. Zheng J, Woo SL, Hu X, Botchlett R, Chen L, Huo Y, Wu C. Metformin and metabolic diseases: a focus on hepatic aspects. Front Med. 2015;9(2):173-86. Disponible en: https://doi.org/10.1007s11684-015-0384-0
15. Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, et al. Anti-inflammatory effects of metformin irrespective of diabetes status. Circ Res. 2016;119(5):652-65. Disponible en: https://doi.org10.1161IRCRESAHA.116.308445
16. Bhatti AB, Usman M. Drug Targets for oxidative podocyte injury in diabetic nephropathy. Cureus. 2015;7(12):e393. Disponible en: https://doi.org/10.7759/cureus.393
17. Anil Kumar P, Welsh GI, Saleem MA, Menon RK. Molecular and cellular events mediating glomerular podocyte dysfunction and depletion in diabetes mellitus. Front Endocrinol (Lausanne). 2014;5:151. Disponible en: https://doi.org/10.3389/fendo.2014.00151
18. Fakhruddin S, Alanazi W, Jackson KE. Diabetes-induced reactive oxygen species: Mechanism of their generation and role in renal injury. J Diabetes Res. 2017;2017:8379327. Disponible en: https://doi.org10.1155/2017/8379327
19. Kim J, Shon E, Kim CS, Kim JS. Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin. Exp Diabetes Res. 2012;2012:210821. Disponible en: https://doi.org/10.11552012/210821
20. Tonneijck L, Smits MM, Muskiet MH, Hoekstra T, Kramer MH, Danser AH, Diamant M, Joles JA, van Raalte DH. Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial. Diabetologia. 2016;59(7):1412-21. Disponible en: https://doi.org/10.1007s00125-016-3938-z
21. Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S, Pfarr E, Woerle HJ, von Eynatten M. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016;59(9):1860-70. Disponible en: https://doi.org/10.1007s00125-016-4008-2
22. Piwkowska A, Rogacka D, Jankowski M, Dominiczak MH, Stepinski JK, Angielski S. Metformin induces suppression of NAD(P) H oxidase activity in podocytes. Biochem Biophys Res Commun. 2010;393(2):268-73.Disponible en: https://doi.org/10.1016/j.bbrc.2010.01.119
23. Ravindran S, Kuruvilla V, Wilbur K, Munusamy S. Nephroprotective effects of metformin in diabetic nephropathy. J Cell Physiol. 2017;232(4):731-42. Disponible en: https://doi.org/10.1002/jcp.25598
24. Preiss D, Dawed A, Welsh P, Heggie A, Jones AG, Dekker J, Koivula R, Hansen TH, Stewart C, Holman RR, Franks PW, Walker M, Pearson ER, Sattar N; Direct consortium group. Sustained influence of metformin therapy on circulating glucagon-like peptide 1 levels in individuals with and without type 2 diabetes. Diabetes Obes Metab. 2017;19(3):356-63. Disponible en: https://doi.org/10.1111/dom.12826
25. DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016;59(8):1645-54. Disponible en: https://doi.org/10.1007/s00125-016-3992-6
26. McCreight LJ, Bailey CJ, Pearson ER. Metformin and the gastrointestinal tract. Diabetologia. 2016;59(3):426-35. Disponible en: https://doi.org/10.1007/s00125-015-3844-9
27. Kim J, Shon E, Kim CS, Kim JS. Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin. Exp Diabetes Res. 2012;2012:210821. Disponible en: https://doi.org/10.11552012/210821
28. Alhaider AA, Korashy HM, Sayed-Ahmed MM, Mobark M, Kfoury H, Mansour MA. Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact. 2011;192(3):233-42. Disponible en: https://doi.org/10.1016/j.cbi.2011.03.014
29. Taheri N, Azarmi Y, Neshat M, Garjani A, Doustar Y. Study the effects of metformin on renal function and structure after unilateral ischemia-reperfusion in rat. Res Pharm Sci. 2012;7:274.
30. Amador-Licona N, Guizar-Mendoza J, Vargas E, Sanchez-Camargo G, Zamora-Mata L. The short-term effect of a switch from glibenclamide to metformin on blood pressure and microalbuminuria in patients with type 2 diabetes mellitus. Arch Med Res. 2000;31:571-5. Disponible en: https://doi.org/10.1016/S0188-4409(00)00241-1
31. Ding Y, Choi ME. Autophagy in diabetic nephropathy. J Endocrinol. 2015;224(1):R15-30. Disponible en: https://doi.org/10.1530/JOE-14-0437
32. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature Cell Biology. 2011;13:132-41. Disponible en: https://doi.org/10.1038/ncb2152
33. Ekstrom N, Schioler L, Svensson AM, et al. Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register. BMJ Open. 2012;2:e001076. Disponible en: https://doi.org10.1136/bmjopen-2012-001076
34. Crowley MJ, Diamantidis CJ, McDuffie JR, Cameron CB, Stanifer JW, Mock CK et al. Clinical outcomes of metformin use in populations with chronic kidney disease, congestive heart failure, or chronic liver disease: A Systematic Review. Ann Intern Med. 2017;166(3):191-200. Disponible en: https://doi.org/10.7326/M16-1901
35. Zeller M, Labalette-Bart M, Juliard JM, Potier L, Feldman LJ, Steg PG et al. Metformin and contrast-induced acute kidney injury in diabetic patients treated with primary percutaneous coronary intervention for ST segment elevation myocardial infarction: A multicenter study. Int J Cardiol. 2016;220:137-42. Disponible en: https://doi.org/10.1016 j.ijcard.2016.06.076
36. Posma RA, Lexis CP, Lipsic E, Nijsten MW, Damman K, Touw DJ et al. Effect of metformin on renal function after primary percutaneous coronary intervention in patients without diabetes Presenting with ST- levation myocardial infarction: Data from the GIPS-III Trial. Cardiovasc Drugs Ther. 2015;29(5):451-9. Disponible en: https://doi.org/10.1007s10557-015-6618-1
37. Nathan DM, Buse JB, Davidson MB, et al.; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203. Disponible en: https://doi.org/10.2337/dc08-9025
38. Miles JM, Rule AD, Borlaug BA. Use of metformin in diseases of aging. Curr Diab Rep. 2014;14:490. Disponible en: https://doi.org/10.1007s11892-014-0490-4
39. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312(24):2668-75. Disponible en: https://doi.org/10.1001jama.2014.15298
40. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-79. Disponible en: https://doi.org/10.2337/dc12-0413
41. Holstein A, Stumvoll M. Contraindications can damage your health: is metformin a case in point? Diabetologia. 2005;48(12):2454-9. Disponible en: https://doi.org/10.2337/dc12-0413
42. Molitch ME, Adler AI, Flyvbjerg A, Nelson RG, So WY, Wanner C, Kasiske BL, Wheeler DC, de Zeeuw D, Mogensen CE. Diabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes. Kidney Int. 2015;87(1):20-30. Disponible en: https://doi.org/10.1038/ki.2014.128
43. Nye HJ, Herrington WG. Metformin: The safest hypoglycaemic agent in chronic kidney disease? Nephron Clin Pract. 2011;118(4):c380-3. Disponible en: https://doi.org/10.1159/000323739
44. Stades AM, Heikens JT, Erkelens DW, Holleman F, Hoekstra JB. Metformin and lactic acidosis: cause or coincidence? A review of case reports. J Intern Med. 2004;255(2):179-87. Disponible en: https://doi.org/10.1046/j.1365-2796.2003.01271.x
45. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-9. Disponible en: https://doi.org/10.1016j.metabol.2015.10.014
46. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010;CD002967:10.1002/14651858.CD002967.pub3
47. 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(8):605-14.
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2. Anand S., Bitton A., Gaziano T. The gap between estimated incidence of end-stage renal disease and use of therapy. PLoS ONE. 2013;8:e72860. Disponible en: https://doi.org/10.1371/journal.pone.0072860
3. Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME. Diabetic kidney disease: a report from an ADA Consensus Conference. Am J Kidney Dis. 2014;64(4):510-33. Disponible en: https://doi.org/10.1053j.ajkd.2014.08.001
4. National Kidney Foundation. KDOQI Clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60(5):850-86. Disponible en: https://doi.org/10.1053/j.ajkd.2012.07.005
5. Lopez-Giacoman S, Madero M. Biomarkers in chronic kidney disease, from kidney function to kidney damage. World J Nephrol. 2015;4(1):57-73. Disponible en: https://doi.org/10.5527/wjn.v4.i1.57
6. Adler AI, Stevens RJ, Manley SE, et al. Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63:225-32. Disponible en: https://doi.org/10.1046/j.1523-1755.2003.00712.x
7. Mora-Fernández C, Domínguez-Pimentel V, de Fuentes MM, Górriz JL, Martínez-Castelao A, Navarro-González JF. Diabetic kidney disease: from physiology to therapeutics. J Physiol. 2014;592(18):3997-4012. Disponible en: https://doi.org/10.1113/jphysiol.2014.272328
8. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 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. Diabetes Care. 2015;38(1):140-9. Disponible en: https://doi.org/10.2337/dc14-2441
9. American Diabetes Association. Pharmacological approaches to glycemic treatment. Diabetes Care, 2017;40(Suppl. 1):S64-74. Disponible en: https://doi.org/10.2337/dc17-S012
10. Anabtawi A, Miles JM. Metformin: Nonglycemic effects and potential novel indications. Endocr Pract. 2016;22(8):999-1007. Disponible en: https://doi.org/10.4158/EP151145.RA
11. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854-65. Disponible en: https://doi.org/10.1016/S0140-6736(98)07037-8
12. US 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. April 8, 2016. Disponible en: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM494140.pdf Accedido: Octubre 12, 2016.
13. European Medicines Agency. Use of metformin to treat diabetes now expanded to patients with moderately reduced kidney function. 14 October 2016. EMA/603690/2016. Disponible en:www.ema.europa.eu/.../index.jsp?curl=pages/news_and_events/news/201610/news_detail_002620.jsp&mid=WC - 45k Accedido: Noviembre 15, 2016.
14. Zheng J, Woo SL, Hu X, Botchlett R, Chen L, Huo Y, Wu C. Metformin and metabolic diseases: a focus on hepatic aspects. Front Med. 2015;9(2):173-86. Disponible en: https://doi.org/10.1007s11684-015-0384-0
15. Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, et al. Anti-inflammatory effects of metformin irrespective of diabetes status. Circ Res. 2016;119(5):652-65. Disponible en: https://doi.org10.1161IRCRESAHA.116.308445
16. Bhatti AB, Usman M. Drug Targets for oxidative podocyte injury in diabetic nephropathy. Cureus. 2015;7(12):e393. Disponible en: https://doi.org/10.7759/cureus.393
17. Anil Kumar P, Welsh GI, Saleem MA, Menon RK. Molecular and cellular events mediating glomerular podocyte dysfunction and depletion in diabetes mellitus. Front Endocrinol (Lausanne). 2014;5:151. Disponible en: https://doi.org/10.3389/fendo.2014.00151
18. Fakhruddin S, Alanazi W, Jackson KE. Diabetes-induced reactive oxygen species: Mechanism of their generation and role in renal injury. J Diabetes Res. 2017;2017:8379327. Disponible en: https://doi.org10.1155/2017/8379327
19. Kim J, Shon E, Kim CS, Kim JS. Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin. Exp Diabetes Res. 2012;2012:210821. Disponible en: https://doi.org/10.11552012/210821
20. Tonneijck L, Smits MM, Muskiet MH, Hoekstra T, Kramer MH, Danser AH, Diamant M, Joles JA, van Raalte DH. Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial. Diabetologia. 2016;59(7):1412-21. Disponible en: https://doi.org/10.1007s00125-016-3938-z
21. Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S, Pfarr E, Woerle HJ, von Eynatten M. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016;59(9):1860-70. Disponible en: https://doi.org/10.1007s00125-016-4008-2
22. Piwkowska A, Rogacka D, Jankowski M, Dominiczak MH, Stepinski JK, Angielski S. Metformin induces suppression of NAD(P) H oxidase activity in podocytes. Biochem Biophys Res Commun. 2010;393(2):268-73.Disponible en: https://doi.org/10.1016/j.bbrc.2010.01.119
23. Ravindran S, Kuruvilla V, Wilbur K, Munusamy S. Nephroprotective effects of metformin in diabetic nephropathy. J Cell Physiol. 2017;232(4):731-42. Disponible en: https://doi.org/10.1002/jcp.25598
24. Preiss D, Dawed A, Welsh P, Heggie A, Jones AG, Dekker J, Koivula R, Hansen TH, Stewart C, Holman RR, Franks PW, Walker M, Pearson ER, Sattar N; Direct consortium group. Sustained influence of metformin therapy on circulating glucagon-like peptide 1 levels in individuals with and without type 2 diabetes. Diabetes Obes Metab. 2017;19(3):356-63. Disponible en: https://doi.org/10.1111/dom.12826
25. DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016;59(8):1645-54. Disponible en: https://doi.org/10.1007/s00125-016-3992-6
26. McCreight LJ, Bailey CJ, Pearson ER. Metformin and the gastrointestinal tract. Diabetologia. 2016;59(3):426-35. Disponible en: https://doi.org/10.1007/s00125-015-3844-9
27. Kim J, Shon E, Kim CS, Kim JS. Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin. Exp Diabetes Res. 2012;2012:210821. Disponible en: https://doi.org/10.11552012/210821
28. Alhaider AA, Korashy HM, Sayed-Ahmed MM, Mobark M, Kfoury H, Mansour MA. Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact. 2011;192(3):233-42. Disponible en: https://doi.org/10.1016/j.cbi.2011.03.014
29. Taheri N, Azarmi Y, Neshat M, Garjani A, Doustar Y. Study the effects of metformin on renal function and structure after unilateral ischemia-reperfusion in rat. Res Pharm Sci. 2012;7:274.
30. Amador-Licona N, Guizar-Mendoza J, Vargas E, Sanchez-Camargo G, Zamora-Mata L. The short-term effect of a switch from glibenclamide to metformin on blood pressure and microalbuminuria in patients with type 2 diabetes mellitus. Arch Med Res. 2000;31:571-5. Disponible en: https://doi.org/10.1016/S0188-4409(00)00241-1
31. Ding Y, Choi ME. Autophagy in diabetic nephropathy. J Endocrinol. 2015;224(1):R15-30. Disponible en: https://doi.org/10.1530/JOE-14-0437
32. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature Cell Biology. 2011;13:132-41. Disponible en: https://doi.org/10.1038/ncb2152
33. Ekstrom N, Schioler L, Svensson AM, et al. Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register. BMJ Open. 2012;2:e001076. Disponible en: https://doi.org10.1136/bmjopen-2012-001076
34. Crowley MJ, Diamantidis CJ, McDuffie JR, Cameron CB, Stanifer JW, Mock CK et al. Clinical outcomes of metformin use in populations with chronic kidney disease, congestive heart failure, or chronic liver disease: A Systematic Review. Ann Intern Med. 2017;166(3):191-200. Disponible en: https://doi.org/10.7326/M16-1901
35. Zeller M, Labalette-Bart M, Juliard JM, Potier L, Feldman LJ, Steg PG et al. Metformin and contrast-induced acute kidney injury in diabetic patients treated with primary percutaneous coronary intervention for ST segment elevation myocardial infarction: A multicenter study. Int J Cardiol. 2016;220:137-42. Disponible en: https://doi.org/10.1016 j.ijcard.2016.06.076
36. Posma RA, Lexis CP, Lipsic E, Nijsten MW, Damman K, Touw DJ et al. Effect of metformin on renal function after primary percutaneous coronary intervention in patients without diabetes Presenting with ST- levation myocardial infarction: Data from the GIPS-III Trial. Cardiovasc Drugs Ther. 2015;29(5):451-9. Disponible en: https://doi.org/10.1007s10557-015-6618-1
37. Nathan DM, Buse JB, Davidson MB, et al.; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203. Disponible en: https://doi.org/10.2337/dc08-9025
38. Miles JM, Rule AD, Borlaug BA. Use of metformin in diseases of aging. Curr Diab Rep. 2014;14:490. Disponible en: https://doi.org/10.1007s11892-014-0490-4
39. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312(24):2668-75. Disponible en: https://doi.org/10.1001jama.2014.15298
40. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-79. Disponible en: https://doi.org/10.2337/dc12-0413
41. Holstein A, Stumvoll M. Contraindications can damage your health: is metformin a case in point? Diabetologia. 2005;48(12):2454-9. Disponible en: https://doi.org/10.2337/dc12-0413
42. Molitch ME, Adler AI, Flyvbjerg A, Nelson RG, So WY, Wanner C, Kasiske BL, Wheeler DC, de Zeeuw D, Mogensen CE. Diabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes. Kidney Int. 2015;87(1):20-30. Disponible en: https://doi.org/10.1038/ki.2014.128
43. Nye HJ, Herrington WG. Metformin: The safest hypoglycaemic agent in chronic kidney disease? Nephron Clin Pract. 2011;118(4):c380-3. Disponible en: https://doi.org/10.1159/000323739
44. Stades AM, Heikens JT, Erkelens DW, Holleman F, Hoekstra JB. Metformin and lactic acidosis: cause or coincidence? A review of case reports. J Intern Med. 2004;255(2):179-87. Disponible en: https://doi.org/10.1046/j.1365-2796.2003.01271.x
45. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-9. Disponible en: https://doi.org/10.1016j.metabol.2015.10.014
46. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010;CD002967:10.1002/14651858.CD002967.pub3
47. 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(8):605-14.
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