Sodium-glucose cotransporter-2 inhibitors in kidney transplant recipients




SGLT2 inhibitors, Kidney transplantation, Kidney outcomes


Several recent randomized controlled trials (RCTs) have demonstrated the broad clinical application of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in improving kidney and cardiovascular outcomes in patients with native kidney disease. In January 2023, Dapagliflozin became the first SGLT2 inhibitor approved by the Italian Medicines Agency Administration (AIFA) for the treatment of chronic kidney disease (CKD) regardless of diabetic status. However, although these agents have received considerable praise for their cardiovascular and nephroprotective effects among patients with native kidney disease, the safety and efficacy of SGLT2i in the kidney transplant setting are not well-known as safety concerns have led to the exclusion of transplant recipients from all large RCTs. This review will discuss the known mechanisms SGLT2i employ to provide their beneficial effects, the potential benefits and risks of these agents in the context of kidney transplantation, and finally, it will examine the current findings of published literature on SGLT2i use in kidney transplant recipients and propose potential directions for future research.


Download data is not yet available.


Wyld M, Morton RL, Hayen A, Howard K, Webster AC. A systematic review and meta-analysis of utility-based quality of life in chronic kidney disease treatments. PLoS Med. 2012;9(9):e1001307. PMID:22984353 DOI:

Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341(23):1725-1730. PMID:10580071 DOI:

Meier-Kriesche HU, Ojo AO, Port FK, Arndorfer JA, Cibrik DM, Kaplan B. Survival improvement among patients with end-stage renal disease: trends over time for transplant recipients and wait-listed patients. J Am Soc Nephrol. 2001;12(6):1293-1296. PMID:11373354 DOI:

Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med. 2000;342(9):605-612. PMID:10699159 DOI:

Foster BJ, Dahhou M, Zhang X, Platt RW, Hanley JA. Change in mortality risk over time in young kidney transplant recipients. Am J Transplant. 2011;11(11):2432-2442. PMID:21831152 DOI:

Lentine KL, Smith JM, Hart A, et al. OPTN/SRTR 2020 Annual Data Report: kidney. Am J Transplant. 2022;22(suppl 2):21-136. PMID:35266618 DOI:

Birdwell KA, Park M. Post-Transplant Cardiovascular Disease. Clin J Am Soc Nephrol. 2021;16(12):1878-1889. PMID:34556500 DOI:

Jenssen T, Hartmann A. Post-transplant diabetes mellitus in patients with solid organ transplants. Nat Rev Endocrinol. 2019;15(3):172-188. PMID:30622369 DOI:

Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3(2):178-185. PMID:12603213 DOI:

Cosio FG, Hickson LJ, Griffin MD, Stegall MD, Kudva Y. Patient survival and cardiovascular risk after kidney transplantation: the challenge of diabetes. Am J Transplant. 2008;8(3):593-599. PMID:1829415511. Sharif A, Hecking M, de Vries AP et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant. 2014 Sep;14(9):1992-2000. PMID: 25307034 DOI:

Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657. PMID:28605608 DOI:

Wiviott SD, Raz I, Bonaca MP, et al; DECLARE–TIMI 58 Investigators. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. PMID:30415602 DOI:

Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. PMID:26378978 DOI:

Cannon CP, Pratley R, Dagogo-Jack S, et al; VERTIS CV Investigators. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020;383(15):1425-1435. PMID:32966714 DOI:

Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. PMID:32970396 DOI:

Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. PMID:30990260 DOI:

McMurray JJV, Solomon SD, Inzucchi SE, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. PMID:31535829 DOI:

Packer M, Anker SD, Butler J, et al; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424. PMID:32865377 DOI:

Cherney DZI, Cosentino F, Dagogo-Jack S, et al; VERTIS CV Investigators. Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial. Clin J Am Soc Nephrol. 2021;16(9):1345-1354. PMID:34497110 DOI:

Wanner C, Inzucchi SE, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-334. PMID:27299675 DOI:

Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018;6(9):691-704. PMID:29937267 DOI:

AlKindi F, Al-Omary HL, Hussain Q, Al Hakim M, Chaaban A, Boobes Y. Outcomes of SGLT2 Inhibitors Use in Diabetic Renal Transplant Patients. Transplant Proc. 2020;52(1):175-178. PMID:31924404 DOI:

Attallah N, Yassine L. Use of Empagliflozin in Recipients of Kidney Transplant: A Report of 8 Cases. Transplant Proc. 2019;51(10):3275-3280. PMID:31732204 DOI:

Halden TAS, Kvitne KE, Midtvedt K, et al. Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus. Diabetes Care. 2019;42(6):1067-1074. PMID:30862658 DOI:

Mahling M, Schork A, Nadalin S, Fritsche A, Heyne N, Guthoff M. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibition in Kidney Transplant Recipients with Diabetes Mellitus. Kidney Blood Press Res. 2019;44(5):984-992. PMID:31437852 DOI:

Rajasekeran H, Kim SJ, Cardella CJ, et al. Use of Canagliflozin in Kidney Transplant Recipients for the Treatment of Type 2 Diabetes: A Case Series. Diabetes Care. 2017;40(7):e75-e76. PMID:28416475 DOI:

Schwaiger E, Burghart L, Signorini L, et al. Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety. Am J Transplant. 2019;19(3):907-919. PMID:30585690 DOI:

Shah M, Virani Z, Rajput P, Shah B. Efficacy and Safety of Canagliflozin in Kidney Transplant Patients. Indian J Nephrol. 2019;29(4):278-281. PMID:31423063 DOI:

Song CC, Brown A, Winstead R, et al. Early initiation of sodium-glucose linked transporter inhibitors (SGLT-2i) and associated metabolic and electrolyte outcomes in diabetic kidney transplant recipients. Endocrinol Diabetes Metab. 2020;4(2):e00185. PMID:33855198 DOI:

kong J, Joon J, Chul Y, et al. SP770 sodium/glucose cotransporter 2 inhibitors for the treatment of diabetes in kidney transplant patients. Nephrol Dial Transplant 2019; 34(Suppl.1). DOI:

Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020;17(12):761-772. PMID:32665641 DOI:

Vallon V, Verma S. Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. Annu Rev Physiol. 2021;83(1):503-528. PMID:33197224 DOI:

Heerspink HJL, Cherney DZI. Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor Initiation. Clin J Am Soc Nephrol. 2021;16(8):1278-1280. PMID:33879500 DOI:

Halimi JM. Low-grade proteinuria and microalbuminuria in renal transplantation. Transplantation. 2013;96(2):121-130. PMID:23435457 DOI:

Halimi JM, Buchler M, Al-Najjar A, et al. Urinary albumin excretion and the risk of graft loss and death in proteinuric and non-proteinuric renal transplant recipients. Am J Transplant. 2007;7(3):618-625. PMID:17217438 DOI:

Formica RN Jr, Friedman AL, Lorber MI, Smith JD, Eisen T, Bia MJ. A randomized trial comparing losartan with amlodipine as initial therapy for hypertension in the early post-transplant period. Nephrol Dial Transplant. 2006;21(5):1389-1394. PMID:16431893 DOI:

Barnett AH, Mithal A, Manassie J, et al; EMPA-REG RENAL trial investigators. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2(5):369-384. PMID:24795251 DOI:

Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85(4):962-971. PMID:24067431 DOI:

Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499-508. PMID:24463454 DOI:

Hoogeveen EK, Aalten J, Rothman KJ, et al. Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up. Transplantation. 2011;91(8):869-874. PMID:21326138 DOI:

Majewski C, Bakris GL. Blood pressure reduction: an added benefit of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes. Diabetes Care. 2015;38(3):429-430. PMID:25715414 DOI:

Tang J, Ye L, Yan Q, Zhang X, Wang L. Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Water and Sodium Metabolism. Front Pharmacol. 2022;13:800490. PMID:35281930 DOI:

Ferrannini E, Baldi S, Frascerra S, et al. Renal Handling of Ketones in Response to Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes. Diabetes Care. 2017;40(6):771-776. PMID:28325783 DOI:

Griffin M, Rao VS, Ivey-Miranda J, et al. Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects. Circulation. 2020;142(11):1028-1039. PMID:32410463 DOI:

Hallow KM, Helmlinger G, Greasley PJ, McMurray JJV, Boulton DW. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab. 2018;20(3):479-487. PMID:29024278 DOI:

Verma A, Patel AB, Waikar SS. SGLT2 Inhibitor: Not a Traditional Diuretic for Heart Failure. Cell Metab. 2020;32(1):13-14. PMID:32640243 DOI:

Oliva RV, Bakris GL. Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors. J Am Soc Hypertens. 2014;8(5):330-339. PMID:24631482 DOI:

Wei R, Wang W, Pan Q, Guo L. Effects of SGLT-2 Inhibitors on Vascular Endothelial Function and Arterial Stiffness in Subjects With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2022;13:826604. PMID:35250882 DOI:

Opelz G, Wujciak T, Ritz E. Association of chronic kidney graft failure with recipient blood pressure. Collaborative Transplant Study. Kidney Int. 1998;53(1):217-222. PMID:9453022 DOI:

Weir MR, Slee A, Sun T, et al. Effects of canagliflozin on serum potassium in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. Clin Kidney J. 2020;14(5):1396-1402. PMID:34221371 DOI:

Zhao Y, Xu L, Tian D, et al. Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2018;20(2):458-462. PMID:28846182 DOI:

Tang H, Zhang X, Zhang J, et al. Elevated serum magnesium associated with SGLT2 inhibitor use in type 2 diabetes patients: a meta-analysis of randomised controlled trials. Diabetologia. 2016;59(12):2546-2551. PMID:27628105 DOI:

Miles CD, Westphal SG. Electrolyte Disorders in Kidney Transplantation. Clin J Am Soc Nephrol. 2020;15(3):412-414. PMID:32066594 DOI:

Clive DM. Renal transplant-associated hyperuricemia and gout. J Am Soc Nephrol. 2000;11(5):974-979. PMID:10770978 DOI:

Inzucchi SE, Zinman B, Fitchett D, et al. How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. 2018;41(2):356-363. PMID:29203583 DOI:

Mazer CD, Hare GMT, Connelly PW, et al. Effect of Empagliflozin on Erythropoietin Levels, Iron Stores, and Red Blood Cell Morphology in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease. Circulation. 2020;141(8):704-707. PMID:31707794 DOI:

Ghanim H, Abuaysheh S, Hejna J, et al. Dapagliflozin Suppresses Hepcidin And Increases Erythropoiesis. J Clin Endocrinol Metab. 2020;105(4):dgaa057. PMID:32044999 DOI:

Yabu JM, Winkelmayer WC. Posttransplantation anemia: mechanisms and management. Clin J Am Soc Nephrol. 2011;6(7):1794-1801. PMID:21734096 DOI:

Schechter A, Gafter-Gvili A, Shepshelovich D, et al. Post renal transplant anemia: severity, causes and their association with graft and patient survival. BMC Nephrol. 2019;20(1):51. PMID:30760235 DOI:

Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;357(25):2601-2614. PMID:18094380 DOI:

Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2018 Annual Data Report: kidney. Am J Transplant. 2020;20(suppl s1):20-130. PMID:31898417 DOI:

Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13507. PMID:30793386 DOI:

Ariza-Heredia EJ, Beam EN, Lesnick TG, Kremers WK, Cosio FG, Razonable RR. Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis. Ann Transplant. 2013;18:195-204. PMID:23792521 DOI:

Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016;18(8):783-794. PMID:27059700 DOI:

Palmer BF, Clegg DJ. Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy. Clin J Am Soc Nephrol. 2021;16(8):1284-1291. PMID:33563658 DOI:

Liu J, Li L, Li S, et al. Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2020;22(9):1619-1627. PMID:32364674 DOI:

Watts NB, Bilezikian JP, Usiskin K, et al. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016;101(1):157-166. PMID:26580237 DOI:

Nadkarni GN, Ferrandino R, Chang A, et al. Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis. Diabetes Care. 2017;40(11):1479-1485. PMID:28827404 DOI:

Chang HY, Singh S, Mansour O, Baksh S, Alexander GC. Association Between Sodium-Glucose Cotransporter 2 Inhibitors and Lower Extremity Amputation Among Patients With Type 2 Diabetes. JAMA Intern Med. 2018;178(9):1190-1198. PMID:30105373 DOI:

Abbott KC, Bernet VJ, Agodoa LY, Yuan CM. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome after renal transplantation in the United States. BMC Endocr Disord. 2003;3(1):1. PMID:12659645 DOI:

Dhatariya KK, Glaser NS, Codner E, Umpierrez GE. Diabetic ketoacidosis. Nat Rev Dis Primers. 2020;6(1):40. PMID:32409703 DOI:

Abuelo JG. Normotensive ischemic acute renal failure. N Engl J Med. 2007;357(8):797-805. PMID:17715412 DOI:

Menne J, Dumann E, Haller H, Schmidt BMW. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002983. PMID:31815931 DOI:

Katsurada K, Nandi SS, Sharma NM, Patel KP. Enhanced Expression and Function of Renal SGLT2 (Sodium-Glucose Cotransporter 2) in Heart Failure: Role of Renal Nerves. Circ Heart Fail. 2021;14(12):e008365. PMID:34789005 DOI:

Katsurada K, Nandi SS, Sharma NM, Patel KP. Role of the renal nerves in regulating SGLT2 inhibitor-induced diuresis and natriuresis in rats with heart failure. FASEB J. 2020;34(S1):1-1. DOI:

Devineni D, Polidori D, Curtin C, Stieltjes H, Tian H, Wajs E. Single-dose Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Selective Inhibitor of Sodium Glucose Cotransporter 2, in Healthy Indian Participants. Clin Ther. 2016;38(1):89-98.e1. PMID:26687552 DOI:

Kaushal S, Singh H, Thangaraju P, Singh J. Canagliflozin: A Novel SGLT2 Inhibitor for Type 2 Diabetes Mellitus. N Am J Med Sci. 2014;6(3):107-113. PMID:24741548 DOI:

Shuster S, Al-Hadhrami Z, Moore S, Awad S, Shamseddin MK. Use of Sodium-Glucose Cotransporter-2 Inhibitors in Renal Transplant Patients With Diabetes: A Brief Review of the Current Literature. Can J Diabetes. 2022;46(2):207-212. PMID:34362679 DOI:

Chewcharat A, Prasitlumkum N, Thongprayoon C, et al. Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis. Med Sci (Basel). 2020;8(4):47. PMID:33213078 DOI:

KwonH, Son SH, Kim K et al. Sodium/glucose cotransporter 2 inhibitors reduce microalbuminuria in diabetic renal transplant patients.. Transplantation 104(S3):p S430. DOI:

Patel N, Hindi J, Farouk SS. Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Transplantation: What Are We Waiting For? Kidney360. 2021;2(7):1174-1178. PMID:35368347 DOI:



How to Cite

Tsalouchos, A. (2023). Sodium-glucose cotransporter-2 inhibitors in kidney transplant recipients. Giornale Di Clinica Nefrologica E Dialisi, 35(1), 73–81.
Received 2023-06-19
Accepted 2023-10-31
Published 2023-11-23


Most read articles by the same author(s)