The Complete Metformin Guide

Episode 282 brings you the COMPLETE guide on metformin! Every possible interaction, MoA, and question has been answered and summarized here on this episode! My goal for this is to truly summarize the full picture of metformin as too many people demonize it for reasons that literally are so insignificant, they should barely even be paid a notice. So with that in mind, get your notepads ready, this one is FULL of information! And yes, a few references for those of you that wish to read further!   REFERENCES 1. Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221–228. [PubMed] 2. Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One. 2013;8(8):e71583. [PMC free article] [PubMed] 3. Cohen RD, Woods HF. Clinical and biochemical aspects of lactic acidosis. Philadelphia: Blackwell Scientific Publications; 1976. 4. Metformin hydrochoride. Boxed warning. [October 6, 2015]. Available at: https://dailymed​.nlm​.nih.gov/dailymed/fda/fdaDrugXsl​.cfm?setid​=b8004451-7b26-425b-b5ea-cbb1b08e30e3&type;=display. 5. 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):2668–2675. [PMC free article] [PubMed] 6. Gan SC, Barr J, Arieff AI, Pearl RG. Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med. 1992;152(11):2333–2336. [PubMed] 7. 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(1):261–269. [PubMed] 8. Kajbaf F, Arnouts P, de Broe M, Lalau JD. Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world. Pharmacoepidemiol Drug Saf. 2013;22(10):1027–1035.[PubMed] 9. Calabrese AT, Coley KC, DaPos SV, Swanson D, Rao RH. Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy. Arch Intern Med. 2002;162(4):434–437. [PubMed] 10. Emslie-Smith AM, Boyle DI, Evans JM, Sullivan F, Morris AD. Contraindications to metformin therapy in patients with Type 2 diabetes--a population-based study of adherence to prescribing guidelines. Diabet Med. 2001;18(6):483–488. [PubMed] 11. 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. [June 16, 2016]. Available at: http://www​.fda.gov/Drugs​/DrugSafety/ucm493244.htm. 12. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med. 2006;354(23):2473–2483. [PubMed] 13. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabtologia. 2015;58(3):429–442. [PubMed] 14. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012;60(5):850–886. [PubMed] 15. Flory JH, Hennessy S. Metformin use reduction in mild to moderate renal impairment: possible inappropriate curbing of use based on food and drug administration contraindications. JAMA Intern Med. 2015;175(3):458–459. [PubMed] 16. 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;(4) CD002967. [PubMed] 17. Organization for Economic Cooperation and Development. [October 20, 2015]. Available at: http://www​.oecd.org/about​/membersandpartners​/list-oecd-member-countries.htm. 18. Eurich DT, Weir DL, Majumdar SR, et al. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail. 2013;6(3):395–402. [PubMed] 19. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461–470. [PubMed] 20. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–612. [PMC free article] [PubMed] 21. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [PMC free article] [PubMed] 22. Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research and Quality; [October 6, 2015]. Available at: http://www​.effectivehealthcare​.ahrq.gov/index​.cfm/search-for-guides-reviews-and-reports​/?pageaction=displayproduct&productid;=318. 23. Santaguida PL, Raina P, Ismaila P. The Development of the McHarm Quality Assessment Scale for adverse events. 2012 24. Viswanathan M, Ansari M, Berkman N. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville (MD): Agency for Healthcare Research and Quality (US); Mar 8, 2012. [October 6, 2015]. Assessing the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions. [Internet] 2008-. Available from: http://www​.ncbi.nlm.nih​.gov/books/NBK91433/ 25. Andersson C, Olesen JB, Hansen PR, et al. Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study. Diabetologia. 2010;53(12):2546–2553. [PubMed] 26. Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28(10):2345–2351. [PubMed] 27. Weir DL, McAlister FA, Senthilselvan A, Minhas-Sandhu JK, Eurich DT. Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study. JACC Heart Fail. 2014;2(6):573–582. [PubMed] 28. Wang Z. Converting odds ratio to relative risk in cohort studies with partial data information. Journal of Statistical Software. 2013;55(5):1–11. 29. Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association between analytic strategy and estimates of treatment outcomes in meta-analyses. JAMA. 2014;312(6):623–630. [PubMed] 30. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188. [PubMed] 31. Knapp G, Hartung J. Improved tests for a random effects meta-regression with a single covariate. Stat Med. 2003;22(17):2693–2710. [PubMed] 32. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–406. [PubMed] 33. 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(8):2291–2295. [PubMed] 34. Eppenga WL, Lalmohamed A, Geerts AF, et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. Diabetes Care. 2014;37(8):2218–2224. [PubMed] 35. Romero SP, Andrey JL, Garcia-Egido A, et al. Metformin therapy and prognosis of patients with heart failure and new-onset diabetes mellitus. A propensity-matched study in the community. Int J Cardiol. 2013;166(2):404–412. [PubMed] 36. Ito H, Ohno Y, Yamauchi T, Kawabata Y, Ikegami H. Efficacy and safety of metformin for treatment of type 2 diabetes in elderly Japanese patients. Geriatr Gerontol Int. 2011;11(1):55–62. [PubMed] 37. Sterner G, Elmståhl S, Frid A, et al. Renal function in a large cohort of metformin treated patients with type 2 diabetes mellitus. British Journal of Diabetes and Vascular Disease. 2012;12(5):227–231. 38. Zhang X, Harmsen WS, Mettler TA, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology. 2014;60(6):2008–2016. [PMC free article] [PubMed] 39. Becquemont L, Bauduceau B, Benattar-Zibi L, et al. Cardiovascular Drugs and Metformin Drug Dosage According to Renal Function in Non-Institutionalized Elderly Patients. Basic Clin Pharmacol Toxicol. 2015[PubMed] 40. Ekström N, Schiöler 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;2:4. Article Number: e001076. [PMC free article] [PubMed] 41. Aguilar D, Chan W, Bozkurt B, Ramasubbu K, Deswal A. Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circulation: Heart Failure. 2011;4(1):53–58. [PMC free article] [PubMed] 42. Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation. 2005;111(5):583–590. [PubMed] 43. Morgan CL, Mukherjee J, Jenkins-Jones S, Holden SE, Currie CJ. Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study. Diabetes Obes Metab. 2014;16(10):957–962. [PubMed] 44. Roussel R, Travert F, Pasquet B, et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med. 2010;170(21):1892–1899. [PubMed] 45. Evans JM, Doney AS, AlZadjali MA, et al. Effect of Metformin on mortality in patients with heart failure and type 2 diabetes mellitus. Am J Cardiol. 2010;106(7):1006–1010. [PubMed] 46. Inzucchi SE, Masoudi FA, Wang Y, et al. Insulin-sensitizing antihyperglycemic drugs and mortality after acute myocardial infarction: insights from the National Heart Care Project. Diabetes Care. 2005;28(7):1680–1689. [PubMed] 47. Shah DD, Fonarow GC, Horwich TB. Metformin therapy and outcomes in patients with advanced systolic heart failure and diabetes. J Card Fail. 2010;16(3):200–206. [PMC free article] [PubMed] 48. Tinetti ME, McAvay G, Trentalange M, Cohen AB, Allore HG. Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study. BMJ. 2015;351:h4984. [PMC free article] [PubMed] 49. Ampuero J, Ranchal I, Nunez D, et al. Metformin inhibits glutaminase activity and protects against hepatic encephalopathy. PloS One. 2012;7(11):e49279. [PMC free article] [PubMed] 50. Nkontchou G, Cosson E, Aout M, et al. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J Clin Endocrinol Metab. 2011;96(8):2601–2608. [PubMed] 51. Blonde L, Rosenstock J, Mooradian AD, Piper BA, Henry D. Glyburide/metformin combination product is safe and efficacious in patients with type 2 diabetes failing sulphonylurea therapy. Diabetes Obes Metab. 2002;4(6):368–375. [PubMed] 52. Cryer DR, Nicholas SP, Henry DH, Mills DJ, Stadel BV. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes Care. 2005;28(3):539–543. [PubMed] 53. Garber AJ, Larsen J, Schneider SH, Piper BA, Henry D. Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes. Diabetes Obes Metab. 2002;4(3):201–208. [PubMed] 54. Gregorio F, Ambrosi F, Manfrini S, et al. Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin. Diabet Med. 1999;16(12):1016–1024. [PubMed] 55. Hanefeld M, Brunetti P, Schernthaner GH, Matthews DR, Charbonnel BH. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care. 2004;27(1):141–147. [PubMed] 56. Marre M, Howlett H, Lehert P, Allavoine T. Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance) in Type 2 diabetic patients inadequately controlled on metformin. Diabet Med. 2002;19(8):673–680. [PubMed] 57. Schweizer A, Dejager S, Bosi E. Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Obes Metab. 2009;11(8):804–812.[PubMed] 58. Bannister CA, Holden SE, Jenkins-Jones S, et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. 2014;16(11):1165–1173. [PubMed] 59. Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care. 2008;31(11):2086–2091. [PMC free article] [PubMed] 60. Huizinga MM, Roumie CL, Greevy RA, et al. Glycemic and weight changes after persistent use of incident oral diabetes therapy: a Veterans Administration retrospective cohort study. Pharmacoepidemiol Drug Saf. 2010;19(11):1108–1112. [PubMed] 61. Leung S, Mattman A, Snyder F, Kassam R, Meneilly G, Nexo E. Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients. Clin Biochem. 2010;43(9):759–760. [PubMed] 62. Roumie CL, Hung AM, Greevy RA, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2012;157(9):601–610. [PMC free article] [PubMed] 63. Wang CP, Lorenzo C, Espinoza SE. Frailty Attenuates the Impact of Metformin on Reducing Mortality in Older Adults with Type 2 Diabetes. J Endocrinol Diabetes Obes. 2014;2(2) [PMC free article] [PubMed] 64. Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009;339:b4731. [PMC free article] [PubMed] 65. American Diabetes Association. Standards of Medical Care in Diabetes--2016. [June 30, 2016]. Available at: http://care​.diabetesjournals​.org/content/39/Supplement_1. 66. Bolen S, Tseng E, Hutfless S, et al. Diabetes Medications for Adults With Type 2 Diabetes: An Update.Rockville (MD): Agency for Healthcare Research and Quality (US); 2016. AHRQ Comparative Effectiveness Reviews. 67. 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):140–149. [PubMed] 68. Tuot DS, Lin F, Shlipak MG, et al. Potential impact of prescribing metformin according to eGFR rather than serum creatinine. Diabetes Care. 2015;38(11):2059–2067. [PMC free article] [PubMed] 69. Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. Jama. 2016;316(3):313–324. [PubMed] 70. MacDonald MR, Eurich DT, Majumdar SR, et al. Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database. Diabetes Care. 2010;33(6):1213–1218. [PMC free article] [PubMed] 71. U.S. Department of Veterans Affairs. Office of Research & Development. VA CSP Study No. 597: Diuretic Comparison Project. [August 29, 2016]. Available at: http://www​.research.va​.gov/programs/csp/597/ 72. Canadian Diabetes Association. Clinical Practice Guidelines: Pharmacotherapy for Type 2 Diabetes. [June 30, 2016]. Available at: http://guidelines​.diabetes​.ca/bloodglucoselowering​/pharmacologyt2-(1) 73. Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012;22(11):820–827. [PMC free article] [PubMed] 74. Weir MA, Gomes T, Mamdani M, et al. Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study. Nephrol Dial Transplant. 2011;26(6):1888–1894. 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