Background/Aims: Although metformin is contraindicated in patients with increased serum creatinine levels (≥1.5 mg/dl in men, ≥1.4 mg/dl in women) in the United States, its use has not been systematically examined in kidney transplant recipients. We aimed to determine the frequency of metformin use and its associations among kidney transplant recipients, and to assess allograft and patient survival associated with metformin use. Methods: In this retrospective cohort study, we linked Scientific Registry of Transplant Recipients data for all incident kidney transplants 2001-2012 and national pharmacy claims (n = 46,914). We compared recipients having one or more pharmacy claims for a metformin-containing product (n = 4,609) and recipients having one or more claims for a non-metformin glucose-lowering agent (n = 42,305). Results: On average, metformin claims were filled later after transplant and were associated with higher estimated glomerular filtration rates before the first claim. Median serum creatinine (mg/dl) levels before the first claim were lower in recipients with metformin claims than in those with non-metformin claims (1.3 [interquartile range 1.0-1.7] vs. 1.6 [1.2-2.5], respectively; p < 0.0001). Metformin was associated with lower adjusted hazards for living donor (0.55, 95% confidence interval 0.38-0.80; p = 0.002) and deceased donor (0.55, 0.44-0.70; p < 0.0001) allograft survival at 3 years posttransplant, and with lower mortality. Conclusions: Despite metformin being contraindicated in renal dysfunction, many kidney transplant recipients receive it, and it is not associated with worse patient or allograft survival.

US Renal Data System: USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2013.
Shah T, Kasravi A, Huang E, Hayashi R, Young B, Cho YW, Bunnapradist S: Risk factors for development of new-onset diabetes mellitus after kidney transplantation. Transplantation 2006;82:1673-1676.
Chakkera HA, Weil EJ, Pham PT, Pomeroy J, Knowler WC: Can new-onset diabetes after kidney transplant be prevented? Diabetes Care 2013;36:1406-1412.
Bristol-Myers Squibb Company: Glucophage (metformin hydrochlorine) Tablets (package insert). Princeton, NJ, USA, 2009.
Duong JK, Roberts DM, Furlong TJ, Kumar SS, Greenfield JR, Kirkpatrick CM, Graham GG, Williams KM, Day RO: Metformin therapy in patients with chronic kidney disease. Diabetes Obes Metab 2012;14:963-965.
Vasisht KP, Chen SC, Peng Y, Bakris GL: Limitations of metformin use in patients with kidney disease: are they warranted? Diabetes Obes Metab 2010;12:1079-1083.
Brown JB, Pedula K, Barzilay J, Herson MK, Latare P: Lactic acidosis rates in type 2 diabetes. Diabetes Care 1998;21:1659-1663.
Renda F, Mura P, Finco G, Ferrazin F, Pani L, Landoni G: Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review. Eur Rev Med Pharmacol Sci 2013;17(suppl 1):45-49.
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;255:179-187.
Salpeter SR, Greyber E, Pasternak GA, Salpeter EE: Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2003;163:2594-2602.
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;22:1027-1035.
Lipska KJ, Bailey CJ, Inzucchi SE: Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 2011;34:1431-1437.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA: 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-1589.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-853.
Sharif A: Should metformin be our antiglycemic agent of choice post-transplantation? Am J Transplant 2011;11:1376-1381.
Leppke S, Leighton T, Zaun D, Chen SC, Skeans M, Israni AK, Snyder JJ, Kasiske BL: Scientific Registry of Transplant Recipients: collecting, analyzing, and reporting data on transplantation in the United States. Transplant Rev (Orlando) 2013;27:50-56.
Lexi-Comp: Lexi-Drugs Online 2014. (accessed November 6, 2014).
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;130:461-470.
Executive summary: standards of medical care in diabetes - 2013. Diabetes Care 2013;36(suppl 1):S4-S10.
Stang M, Wysowski DK, Butler-Jones D: Incidence of lactic acidosis in metformin users. Diabetes Care 1999;22:925-927.
Bailey CJ, Nattrass M: Treatment-metformin. Baillieres Clin Endocrinol Metab 1988;2:455-476.
Sambol NC, Chiang J, Lin ET, Goodman AM, Liu CY, Benet LZ, Cogan MG: Kidney function and age are both predictors of pharmacokinetics of metformin. J Clin Pharmacol 1995;35:1094-1102.
Kurian B, Joshi R, Helmuth A: Effectiveness and long-term safety of thiazolidinediones and metformin in renal transplant recipients. Endocr Pract 2008;14:979-984.
Salvadori M, Bertoni E, Rosati A, Zanazzi M: Post-transplant diabetes mellitus. J Nephrol 2003;16:626-634.
Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE: Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 1995;333:550-554.
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