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Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease: a systematic review and meta-analysis

  • Nephrology - Review
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Abstract

Purpose

Owing to the pharmacological mechanism, sodium–glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no systematic review or meta-analysis addressed chronic kidney disease (CKD) patients specifically. We aimed to assess the efficacy and safety of SGLT2is in CKD patients.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials. Mean difference (MD) were pooled for the decline of glomerular filtration rate (eGFR) and change in urine albumin-to-creatinine ratio (uACR). Hazard ratio (HR) and rate ratio (RR) were pooled for composite of renal outcomes and adverse effects.

Results

Thirty articles were identified. Overall MD in rate of eGFR decline was 0.02 (P = 0.05), with a borderline significant difference favoring SGLT2is, while the change in uACR from baseline was − 141.34 mg/g and hazard ratio of composite renal outcomes was 0.64 significantly favoring SGLT2is. Subgroup analyses showed that the long-term renal function, participants with baseline macroalbuminuria, and stage 4 CKD patients had significantly slower eGFR decline rate in SGLT2is compared to the placebo group. Risks of genital mycotic infection and ketoacidosis were significantly higher among the SGLT2is group than placebo.

Conclusion

For CKD patients, no matter diabetic or non-diabetic, our study showed potential renoprotective effects favoring SGLT2is in overall and long-term phase, and in patients with macroalbuminuria or stage 4 CKD. However, only slight increased risk of adverse effects among the SGLT2is group is observed. Therefore, we concluded that in CKD patients, prescribing SGLT2is was safe and had renal benefits.

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Data availability

Datasets generated and analyzed in this study are available on reasonable request from the corresponding author.

References

  1. Kovesdy CP (2011) (2022) Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl 12(1):7–11. https://doi.org/10.1016/j.kisu.2021.11.003

    Article  Google Scholar 

  2. Overview: Dapagliflozin for treating chronic kidney disease: guidance. NICE. https://www.nice.org.uk/guidance/ta775. Accessed 18 February

  3. Overview: Chronic kidney disease: assessment and management: guidance. NICE. https://www.nice.org.uk/guidance/ng203. Accessed 18 February

  4. FDA approves treatment for chronic kidney disease. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chronic-kidney-disease. Accessed 18 February 2023

  5. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373(22):2117–2128. https://doi.org/10.1056/NEJMoa1504720

    Article  CAS  PubMed  Google Scholar 

  6. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR (2017) Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 377(7):644–657. https://doi.org/10.1056/NEJMoa1611925

    Article  CAS  PubMed  Google Scholar 

  7. Zhao Z, Jin P, Zhang Y, Hu X, Tian C, Liu D (2022) SGLT2 inhibitors in diabetic patients with cardiovascular disease or at high cardiovascular risk: a systematic review and meta-analysis of randomized controlled trials. Front Cardiovasc Med 9:826684. https://doi.org/10.3389/fcvm.2022.826684

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  8. Lo KB, Gul F, Ram P, Kluger AY, Tecson KM, McCullough PA, Rangaswami J (2020) The effects of SGLT2 inhibitors on cardiovascular and renal outcomes in diabetic patients: a systematic review and meta-analysis. Cardiorenal Med 10(1):1–10. https://doi.org/10.1159/000503919

    Article  CAS  PubMed  Google Scholar 

  9. Zelniker TA, Raz I, Mosenzon O, Dwyer JP, Heerspink H, Cahn A, Goodrich EL, Im K, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Gause-Nilsson I, Langkilde AM, Sabatine MS, Wiviott SD (2021) Effect of dapagliflozin on cardiovascular outcomes according to baseline kidney function and albuminuria status in patients with type 2 diabetes: a prespecified secondary analysis of a randomized clinical trial. JAMA Cardiol 6(7):801–810. https://doi.org/10.1001/jamacardio.2021.0660

    Article  PubMed  Google Scholar 

  10. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Furtado RHM, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS (2019) SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 393(10166):31–39. https://doi.org/10.1016/s0140-6736(18)32590-x

    Article  CAS  PubMed  Google Scholar 

  11. Neuen BL, Young T, Heerspink HJL, Neal B, Perkovic V, Billot L, Mahaffey KW, Charytan DM, Wheeler DC, Arnott C, Bompoint S, Levin A, Jardine MJ (2019) SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 7(11):845–854. https://doi.org/10.1016/s2213-8587(19)30256-6

    Article  CAS  PubMed  Google Scholar 

  12. Weir MR (2016) The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors. Postgrad Med 128(3):290–298. https://doi.org/10.1080/00325481.2016.1147926

    Article  PubMed  Google Scholar 

  13. Ma Y, Lin C, Cai X, Hu S, Zhu X, Lv F, Yang W, Ji L (2023) Baseline eGFR, albuminuria and renal outcomes in patients with SGLT2 inhibitor treatment: an updated meta-analysis. Acta Diabetol 60(3):435–445. https://doi.org/10.1007/s00592-022-02022-7

    Article  CAS  PubMed  Google Scholar 

  14. Wang C, Zhou Y, Kong Z, Wang X, Lv W, Geng Z, Wang Y (2019) The renoprotective effects of sodium-glucose cotransporter 2 inhibitors versus placebo in patients with type 2 diabetes with or without prevalent kidney disease: A systematic review and meta-analysis. Diabetes Obes Metab 21(4):1018–1026. https://doi.org/10.1111/dom.13620

    Article  CAS  PubMed  Google Scholar 

  15. Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou F-F, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde A-M, Wheeler DC (2020) Dapagliflozin in patients with chronic kidney disease. N Engl J Med 383(15):1436–1446. https://doi.org/10.1056/NEJMoa2024816

    Article  CAS  PubMed  Google Scholar 

  16. Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Inzucchi SE, Kosiborod MN, Cherney DZI, Dwyer JP, Scirica BM, Bailey CJ, Díaz R, Ray KK, Udell JA, Lopes RD, Lapuerta P, Steg PG (2021) Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med 384(2):129–139. https://doi.org/10.1056/NEJMoa2030186

    Article  CAS  PubMed  Google Scholar 

  17. Cherney DZI, Dekkers CCJ, Barbour SJ, Cattran D, Abdul Gafor AH, Greasley PJ, Laverman GD, Lim SK, Di Tanna GL, Reich HN, Vervloet MG, Wong MG, Gansevoort RT, Heerspink HJL (2020) Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial. Lancet Diabetes Endocrinol 8(7):582–593. https://doi.org/10.1016/s2213-8587(20)30162-5

    Article  CAS  PubMed  Google Scholar 

  18. Heerspink HJL, Greene T, Tighiouart H, Gansevoort RT, Coresh J, Simon AL, Chan TM, Hou FF, Lewis JB, Locatelli F, Praga M, Schena FP, Levey AS, Inker LA (2019) Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. Lancet Diabetes Endocrinol 7(2):128–139. https://doi.org/10.1016/s2213-8587(18)30314-0

    Article  CAS  PubMed  Google Scholar 

  19. Pollock C, Stefánsson B, Reyner D, Rossing P, Sjöström CD, Wheeler DC, Langkilde AM, Heerspink HJL (2019) Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 7(6):429–441. https://doi.org/10.1016/s2213-8587(19)30086-5

    Article  CAS  PubMed  Google Scholar 

  20. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials (2022). Lancet 400(10365):1788–1801. https://doi.org/10.1016/s0140-6736(22)02074-8

  21. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71

  22. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng H-Y, Corbett MS, Eldridge SM, Emberson JR, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898

  23. Higgins JPT TJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (2022) Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022). Cochrane

  24. Guevara JP, Berlin JA, Wolf FM (2004) Meta-analytic methods for pooling rates when follow-up duration varies: a case study. BMC Med Res Methodol 4:17. https://doi.org/10.1186/1471-2288-4-17

    Article  PubMed  PubMed Central  Google Scholar 

  25. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu P-L, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW (2019) Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380(24):2295–2306. https://doi.org/10.1056/NEJMoa1811744

    Article  CAS  PubMed  Google Scholar 

  26. Jhund PS, Solomon SD, Docherty KF, Heerspink HJL, Anand IS, Böhm M, Chopra V, de Boer RA, Desai AS, Ge J, Kitakaze M, Merkley B, O’Meara E, Shou M, Tereshchenko S, Verma S, Vinh PN, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Langkilde AM, Sjöstrand M, McMurray JJV (2021) Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: results of DAPA-HF. Circulation 143(4):298–309. https://doi.org/10.1161/circulationaha.120.050391

    Article  CAS  PubMed  Google Scholar 

  27. Mc Causland FR, Claggett BL, Vaduganathan M, Desai AS, Jhund P, de Boer RA, Docherty K, Fang J, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, Saraiva JFK, McGrath MM, Shah SJ, Verma S, Langkilde AM, Petersson M, McMurray JJV, Solomon SD (2023) Dapagliflozin and kidney outcomes in patients with heart failure with mildly reduced or preserved ejection fraction: a prespecified analysis of the DELIVER randomized clinical trial. JAMA Cardiol 8(1):56–65. https://doi.org/10.1001/jamacardio.2022.4210

    Article  PubMed  Google Scholar 

  28. Wanner C, Inzucchi SE, Zinman B, Koitka-Weber A, Mattheus M, George JT, von Eynatten M, Hauske SJ (2020) Consistent effects of empagliflozin on cardiovascular and kidney outcomes irrespective of diabetic kidney disease categories: Insights from the EMPA-REG OUTCOME trial. Diabetes Obes Metab 22(12):2335–2347. https://doi.org/10.1111/dom.14158

    Article  CAS  PubMed  Google Scholar 

  29. Voors AA, Damman K, Teerlink JR, Angermann CE, Collins SP, Kosiborod M, Biegus J, Ferreira JP, Nassif ME, Psotka MA, Tromp J, Brueckmann M, Blatchford JP, Salsali A, Ponikowski P (2022) Renal effects of empagliflozin in patients hospitalized for acute heart failure: from the EMPULSE trial. Eur J Heart Fail 24(10):1844–1852. https://doi.org/10.1002/ejhf.2681

    Article  CAS  PubMed  Google Scholar 

  30. Cherney DZI, Charbonnel B, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley R, Shih WJ, Frederich R, Maldonado M, Pong A, Cannon CP (2021) Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial. Diabetologia 64(6):1256–1267. https://doi.org/10.1007/s00125-021-05407-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Shaw W, Barrett TD, Weidner-Wells M, Deng H, Matthews DR, Neal B (2018) Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol 6(9):691–704. https://doi.org/10.1016/s2213-8587(18)30141-4

    Article  CAS  PubMed  Google Scholar 

  32. Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R (2022) Empagliflozin in patients with chronic kidney disease. N Engl J Med. https://doi.org/10.1056/NEJMoa2204233

    Article  PubMed  PubMed Central  Google Scholar 

  33. Cherney DZI, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley R, Frederich R, Maldonado M, Liu C-C, Liu J, Pong A, Cannon CPobotVCVI (2021) Ertugliflozin and slope of chronic eGFR: prespecified analyses from the randomized VERTIS CV trial. Clin J Am Soc Nephrol 16(9)

  34. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G (2005) Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 67(6):2089–2100. https://doi.org/10.1111/j.1523-1755.2005.00365.x

    Article  PubMed  Google Scholar 

  35. Song F, Khan KS, Dinnes J, Sutton AJ (2002) Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy. Int J Epidemiol 31(1):88–95. https://doi.org/10.1093/ije/31.1.88

    Article  PubMed  Google Scholar 

  36. Cochran WG (1950) The comparison of percentages in matched samples. Biometrika 37(3/4):256–266. https://doi.org/10.2307/2332378

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  37. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Bmj 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  38. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. https://doi.org/10.1002/sim.1186

    Article  PubMed  Google Scholar 

  39. (2020) Review Manager (RevMan) [Computer program]. Version 5.4. The Cochrane Collaboration, 2020

  40. Wada T, Mori-Anai K, Takahashi A, Matsui T, Inagaki M, Iida M, Maruyama K, Tsuda H (2022) Effect of canagliflozin on the decline of estimated glomerular filtration rate in chronic kidney disease patients with type 2 diabetes mellitus: a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase III study in Japan. J Diabetes Investig 13(12):1981–1989. https://doi.org/10.1111/jdi.13888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cherney DZI, Ferrannini E, Umpierrez GE, Peters AL, Rosenstock J, Carroll AK, Lapuerta P, Banks P, Agarwal R (2021) Efficacy and safety of sotagliflozin in patients with type 2 diabetes and severe renal impairment. Diabetes Obes Metab 23(12):2632–2642. https://doi.org/10.1111/dom.14513

    Article  CAS  PubMed  Google Scholar 

  42. Chertow GM, Vart P, Jongs N, Toto RD, Gorriz JL, Hou FF, McMurray JJV, Correa-Rotter R, Rossing P, Sjöström CD, Stefánsson BV, Langkilde AM, Wheeler DC, Heerspink HJL (2021) Effects of dapagliflozin in stage 4 chronic kidney disease. J Am Soc Nephrol 32(9):2352–2361. https://doi.org/10.1681/asn.2021020167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bakris G, Oshima M, Mahaffey KW, Agarwal R, Cannon CP, Capuano G, Charytan DM, de Zeeuw D, Edwards R, Greene T, Heerspink HJL, Levin A, Neal B, Oh R, Pollock C, Rosenthal N, Wheeler DC, Zhang H, Zinman B, Jardine MJ, Perkovic V (2020) Effects of canagliflozin in patients with baseline eGFR <30 ml/min per 1.73 m(2): subgroup analysis of the randomized CREDENCE trial. Clin J Am Soc Nephrol 15(12):1705–1714. https://doi.org/10.2215/cjn.10140620

  44. Grunberger G, Camp S, Johnson J, Huyck S, Terra SG, Mancuso JP, Jiang ZW, Golm G, Engel SS, Lauring B (2018) Ertugliflozin in patients with stage 3 chronic kidney disease and type 2 diabetes mellitus: the VERTIS RENAL randomized study. Diabetes Ther 9(1):49–66. https://doi.org/10.1007/s13300-017-0337-5

    Article  CAS  PubMed  Google Scholar 

  45. Takashima H, Yoshida Y, Nagura C, Furukawa T, Tei R, Maruyama T, Maruyama N, Abe M (2018) Renoprotective effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, in type 2 diabetes patients with chronic kidney disease: a randomized open-label prospective trial. Diab Vasc Dis Res 15(5):469–472. https://doi.org/10.1177/1479164118782872

    Article  CAS  PubMed  Google Scholar 

  46. Zannad F, Ferreira JP, Pocock SJ, Zeller C, Anker SD, Butler J, Filippatos G, Hauske SJ, Brueckmann M, Pfarr E, Schnee J, Wanner C, Packer M (2021) Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: insights from EMPEROR-reduced. Circulation 143(4):310–321. https://doi.org/10.1161/circulationaha.120.051685

    Article  CAS  PubMed  Google Scholar 

  47. Mosenzon O, Raz I, Wiviott SD, Schechter M, Goodrich EL, Yanuv I, Rozenberg A, Murphy SA, Zelniker TA, Langkilde AM, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Wilding JPH, McGuire DK, Bhatt DL, Leiter LA, Cahn A, Dwyer JP, Heerspink HJL, Sabatine MS (2022) Dapagliflozin and prevention of kidney disease among patients with type 2 diabetes: post hoc analyses from the DECLARE-TIMI 58 trial. Diabetes Care 45(10):2350–2359. https://doi.org/10.2337/dc22-0382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mosenzon O, Wiviott SD, Cahn A, Rozenberg A, Yanuv I, Goodrich EL, Murphy SA, Heerspink HJL, Zelniker TA, Dwyer JP, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Kato ET, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS, Raz I (2019) Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol 7(8):606–617. https://doi.org/10.1016/s2213-8587(19)30180-9

    Article  CAS  PubMed  Google Scholar 

  49. Neuen BL, Ohkuma T, Neal B, Matthews DR, de Zeeuw D, Mahaffey KW, Fulcher G, Blais J, Li Q, Jardine MJ, Perkovic V, Wheeler DC (2021) Relative and absolute risk reductions in cardiovascular and kidney outcomes with canagliflozin across KDIGO risk categories: findings from the CANVAS program. Am J Kidney Dis 77(1):23-34.e21. https://doi.org/10.1053/j.ajkd.2020.06.018

    Article  CAS  PubMed  Google Scholar 

  50. Levin A, Perkovic V, Wheeler DC, Hantel S, George JT, von Eynatten M, Koitka-Weber A, Wanner C (2020) Empagliflozin and cardiovascular and kidney outcomes across KDIGO risk categories: post hoc analysis of a randomized, double-blind, placebo-controlled, multinational trial. Clin J Am Soc Nephrol 15(10):1433–1444. https://doi.org/10.2215/cjn.14901219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375(4):323–334. https://doi.org/10.1056/NEJMoa1515920

    Article  CAS  PubMed  Google Scholar 

  52. Allegretti AS, Zhang W, Zhou W, Thurber TK, Rigby SP, Bowman-Stroud C, Trescoli C, Serusclat P, Freeman MW, Halvorsen YC (2019) Safety and effectiveness of bexagliflozin in patients with type 2 diabetes mellitus and stage 3a/3b CKD. Am J Kidney Dis 74(3):328–337. https://doi.org/10.1053/j.ajkd.2019.03.417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fioretto P, Del Prato S, Buse JB, Goldenberg R, Giorgino F, Reyner D, Langkilde AM, Sjöström CD, Sartipy P (2018) Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): the DERIVE study. Diabetes Obes Metab 20(11):2532–2540. https://doi.org/10.1111/dom.13413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Barnett AH, Mithal A, Manassie J, Jones R, Rattunde H, Woerle HJ, Broedl UC (2014) 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 2(5):369–384. https://doi.org/10.1016/s2213-8587(13)70208-0

    Article  CAS  PubMed  Google Scholar 

  55. Kohan DE, Fioretto P, Tang W, List JF (2014) 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 85(4):962–971. https://doi.org/10.1038/ki.2013.356

    Article  CAS  PubMed  Google Scholar 

  56. Yale JF, Bakris G, Cariou B, Nieto J, David-Neto E, Yue D, Wajs E, Figueroa K, Jiang J, Law G, Usiskin K, Meininger G (2014) Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes mellitus and chronic kidney disease. Diabetes Obes Metab 16(10):1016–1027. https://doi.org/10.1111/dom.12348

    Article  CAS  PubMed  Google Scholar 

  57. Hovind P, Rossing P, Tarnow L, Smidt UM, Parving HH (2001) Progression of diabetic nephropathy. Kidney Int 59(2):702–709. https://doi.org/10.1046/j.1523-1755.2001.059002702.x

    Article  CAS  PubMed  Google Scholar 

  58. Mogensen CE (1976) Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment. Scand J Clin Lab Invest 36(4):383–388. https://doi.org/10.1080/00365517609055274

    Article  CAS  PubMed  Google Scholar 

  59. Parving HH, Smidt UM, Friisberg B, Bonnevie-Nielsen V, Andersen AR (1981) A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia 20(4):457–461. https://doi.org/10.1007/bf00253407

    Article  CAS  PubMed  Google Scholar 

  60. Viberti GC, Bilous RW, Mackintosh D, Keen H (1983) Monitoring glomerular function in diabetic nephropathy. A prospective study. Am J Med 74(2):256–264. https://doi.org/10.1016/0002-9343(83)90624-1

    Article  CAS  PubMed  Google Scholar 

  61. Lorenzo V, Saracho R, Zamora J, Rufino M, Torres A (2010) Similar renal decline in diabetic and non-diabetic patients with comparable levels of albuminuria. Nephrol Dial Transplant 25(3):835–841. https://doi.org/10.1093/ndt/gfp475

    Article  CAS  PubMed  Google Scholar 

  62. Rossing P, Hougaard P, Parving HH (2005) Progression of microalbuminuria in type 1 diabetes: ten-year prospective observational study. Kidney Int 68(4):1446–1450. https://doi.org/10.1111/j.1523-1755.2005.00556.x

    Article  PubMed  Google Scholar 

  63. Podestà MA, Sabiu G, Galassi A, Ciceri P, Cozzolino M (2023) SGLT2 inhibitors in diabetic and non-diabetic chronic kidney disease. Biomedicines 11(2):279

    Article  PubMed  PubMed Central  Google Scholar 

  64. Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M (2014) Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 129(5):587–597. https://doi.org/10.1161/circulationaha.113.005081

    Article  CAS  PubMed  Google Scholar 

  65. Heerspink HJL, Cherney DZI (2021) Clinical implications of an acute dip in eGFR after SGLT2 inhibitor initiation. Clin J Am Soc Nephrol 16(8):1278–1280. https://doi.org/10.2215/cjn.02480221

    Article  PubMed  PubMed Central  Google Scholar 

  66. Perlman A, Heyman SN, Matok I, Stokar J, Muszkat M, Szalat A (2017) Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: analysis of the FDA adverse event report system database. Nutr Metab Cardiovasc Dis 27(12):1108–1113. https://doi.org/10.1016/j.numecd.2017.10.011

    Article  CAS  PubMed  Google Scholar 

  67. Sridhar VS, Tuttle KR, Cherney DZI (2020) We can finally stop worrying about SGLT2 inhibitors and acute kidney injury. Am J Kidney Dis 76(4):454–456. https://doi.org/10.1053/j.ajkd.2020.05.014

    Article  PubMed  Google Scholar 

  68. Li N, Lv D, Zhu X, Wei P, Gui Y, Liu S, Zhou E, Zheng M, Zhou D, Zhang L (2021) Effects of SGLT2 inhibitors on renal outcomes in patients with chronic kidney disease: a meta-analysis. Front Med. https://doi.org/10.3389/fmed.2021.728089

    Article  PubMed  PubMed Central  Google Scholar 

  69. Panchapakesan U, Pegg K, Gross S, Komala MG, Mudaliar H, Forbes J, Pollock C, Mather A (2013) Effects of SGLT2 inhibition in human kidney proximal tubular cells–renoprotection in diabetic nephropathy? PLoS One 8(2):e54442. https://doi.org/10.1371/journal.pone.0054442

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  70. Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB (2014) Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens 8(4):262-275.e269. https://doi.org/10.1016/j.jash.2014.01.007

    Article  CAS  PubMed  Google Scholar 

  71. Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J (2013) Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab 15(9):853–862. https://doi.org/10.1111/dom.12127

    Article  CAS  PubMed  Google Scholar 

  72. Lytvyn Y, Škrtić M, Yang GK, Yip PM, Perkins BA, Cherney DZ (2015) Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus. Am J Physiol Renal Physiol 308(2):F77-83. https://doi.org/10.1152/ajprenal.00555.2014

    Article  CAS  PubMed  Google Scholar 

  73. Yu B, Dong C, Hu Z, Liu B (2021) Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: a protocol for systematic review and meta-analysis. Medicine (Baltimore) 100(8):e24655. https://doi.org/10.1097/md.0000000000024655

    Article  CAS  PubMed  Google Scholar 

  74. Liu M, Li XC, Lu L, Cao Y, Sun RR, Chen S, Zhang PY (2014) Cardiovascular disease and its relationship with chronic kidney disease. Eur Rev Med Pharmacol Sci 18(19):2918–2926

    CAS  PubMed  Google Scholar 

  75. Levey AS, Gansevoort RT, Coresh J, Inker LA, Heerspink HL, Grams ME, Greene T, Tighiouart H, Matsushita K, Ballew SH, Sang Y, Vonesh E, Ying J, Manley T, de Zeeuw D, Eckardt KU, Levin A, Perkovic V, Zhang L, Willis K (2020) Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the National Kidney Foundation in Collaboration with the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis 75(1):84–104. https://doi.org/10.1053/j.ajkd.2019.06.009

    Article  CAS  PubMed  Google Scholar 

  76. Hu S, Lin C, Cai X, Zhu X, Lv F, Yang W, Ji L (2022) Disparities in efficacy and safety of sodium-glucose cotransporter 2 inhibitor among patients with different extents of renal dysfunction: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 13:1018720. https://doi.org/10.3389/fphar.2022.1018720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Coresh J, Turin TC, Matsushita K, Sang Y, Ballew SH, Appel LJ, Arima H, Chadban SJ, Cirillo M, Djurdjev O, Green JA, Heine GH, Inker LA, Irie F, Ishani A, Ix JH, Kovesdy CP, Marks A, Ohkubo T, Shalev V, Shankar A, Wen CP, de Jong PE, Iseki K, Stengel B, Gansevoort RT, Levey AS (2014) Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. JAMA 311(24):2518–2531. https://doi.org/10.1001/jama.2014.6634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Grams ME, Sang Y, Ballew SH, Matsushita K, Astor BC, Carrero JJ, Chang AR, Inker LA, Kenealy T, Kovesdy CP (2019) Evaluating glomerular filtration rate slope as a surrogate end point for ESKD in clinical trials: an individual participant meta-analysis of observational data. vol 30. Am Soc Nephrol 9:1746–1755. https://doi.org/10.1681/ASN.2019010008

    Article  Google Scholar 

  79. Scheen AJ (2019) An update on the safety of SGLT2 inhibitors. Expert Opin Drug Saf 18(4):295–311. https://doi.org/10.1080/14740338.2019.1602116

    Article  CAS  PubMed  Google Scholar 

  80. Li D, Wang T, Shen S, Fang Z, Dong Y, Tang H (2017) Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 19(3):348–355. https://doi.org/10.1111/dom.12825

    Article  CAS  PubMed  Google Scholar 

  81. Geerlings S, Fonseca V, Castro-Diaz D, List J, Parikh S (2014) Genital and urinary tract infections in diabetes: impact of pharmacologically-induced glucosuria. Diabetes Res Clin Pract 103(3):373–381. https://doi.org/10.1016/j.diabres.2013.12.052

    Article  CAS  PubMed  Google Scholar 

  82. Liu J, Li L, Li S, Jia P, Deng K, Chen W, Sun X (2017) Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep 7(1):2824–2824. https://doi.org/10.1038/s41598-017-02733-w

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  83. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang C-E, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde A-M (2019) Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 381(21):1995–2008. https://doi.org/10.1056/NEJMoa1911303

    Article  CAS  PubMed  Google Scholar 

  84. McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA (2012) Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 35(9):1897–1901. https://doi.org/10.2337/dc11-2054

    Article  PubMed  PubMed Central  Google Scholar 

  85. Horii T, Oikawa Y, Kunisada N, Shimada A, Atsuda K (2020) Real-world risk of hypoglycemia-related hospitalization in Japanese patients with type 2 diabetes using SGLT2 inhibitors: a nationwide cohort study. BMJ Open Diabetes Res Care. https://doi.org/10.1136/bmjdrc-2020-001856

    Article  PubMed  PubMed Central  Google Scholar 

  86. Plewa MC BM, King-Thiele R (2022) Euglycemic diabetic ketoacidosis. StatPearls

  87. Rosenstock J, Ferrannini E (2015) Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care 38(9):1638–1642. https://doi.org/10.2337/dc15-1380

    Article  CAS  PubMed  Google Scholar 

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Funding

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Author notes

  1. Chu-Hsuan Shiau, Li-Yun Tsau, and Chih-Chin Kao contributed equally to this paper. Also, Jeng‑Cheng Wu and Wen-Hsuan Hou contributed equally to this paper.

Authors and Affiliations

  1. Department of Education, Taipei Medical University Hospital, Taipei, Taiwan

    Chu-Hsuan Shiau, Yu-Ching Peng & Jeng‑Cheng Wu

  2. Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan

    Chu-Hsuan Shiau & Jeng‑Cheng Wu

  3. Graduate Institute of Clinical Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan

    Li-Yun Tsau

  4. Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Chih-Chin Kao

  5. Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei, Taiwan

    Chih-Chin Kao & Jeng‑Cheng Wu

  6. Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan

    Chih-Chin Kao

  7. School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan

    Chyi-Huey Bai

  8. Department of Education and Humanities in Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Jeng‑Cheng Wu

  9. Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Wen-Hsuan Hou

  10. Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan

    Wen-Hsuan Hou

  11. International Ph.D. Program in Gerontology and Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan

    Wen-Hsuan Hou

  12. Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei, Taiwan

    Wen-Hsuan Hou

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  1. Chu-Hsuan Shiau
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  7. Wen-Hsuan Hou
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Contributions

Drafted study protocol: LYT; performed electronic database search: LYT, CHS; screened the citations retrieved from electronic searches: LYT, CHS; consulted on discrepancies during screening and data extraction: WHH; performed data extraction: LYT, CHS; performed data synthesis and analysis: LYT, CHS, YCP, CHB; data interpretation: LYT, CHS; writing and drafting: LYT, CHS; reviewing and editing: LYT, CHS, CCK, JCW, WHH; revising and replying to reviewers’ comment: CCK, YCP, JCW, WHH; supervision: CCK, CHB, JCW, WHH. All authors read and approved the final version of the manuscript.

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Correspondence to Jeng‑Cheng Wu or Wen-Hsuan Hou.

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Shiau, CH., Tsau, LY., Kao, CC. et al. Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease: a systematic review and meta-analysis. Int Urol Nephrol 56, 1359–1381 (2024). https://doi.org/10.1007/s11255-023-03789-6

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