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International Urology and Nephrology

Published in:

01-04-2019 | Sulfonylurea | Nephrology - Review

Effect of SGLT2 inhibitor on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

Authors: Chaojie Feng, Minxiang Wu, Zhengyue Chen, Xiongwei Yu, Zhenyu Nie, Yu Zhao, Beiyan Bao

Published in: International Urology and Nephrology | Issue 4/2019

Abstract

Objective

This study summarizes the evidence from randomized controlled trials (RCTs) to assess the effects of SGLT2 inhibitors on renal function and albuminuria in patients with type 2 diabetes.

Materials/methods

We searched PubMed, Web of Science, Cochrane Library and EMBASE for reports published up to March 2018 and included RCTs reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (UACR) changes. Data extraction and assessment of research quality based on Cochrane risk biasing tools. Data were calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95% confidence intervals (CIs) were pooled using a random effects model.

Results

Fifty-one studies were included that evaluated eGFR levels, and 17 studies were included that evaluated UACR levels. A meta-analysis showed that SGLT2 inhibitors had no significant effect on eGFR levels (SMD − 0.02, 95% CI − 0.06, 0.03, p = 0.45), and eGFR reduction was observed in the subsets of the duration of the trial 12 < duration ≤ 26 weeks (SMD − 0.08, 95% CI − 0.13, − 0.02, p = 0.005) and mean baseline eGFR < 60 ml/min per 1.73 square meters (SMD − 0.22, 95% CI − 0.37, − 0.07, p = 0.004). We found that SGLT2 inhibitors reduced UACR levels in patients with type 2 diabetes (SMD − 0.11, 95% CI − 0.17, − 0.05, p = 0.0001). Compared with monotherapy, the combination with other hypoglycemic agents can reduce albuminuria levels (SMD − 0.13, 95% CI − 0.19, − 0.06, p < 0.0001).

Conclusions

The effect of SGLT2 inhibitor on eGFR in patients with T2DM was not statistically significant, but it was effective in reducing albuminuria levels.

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International Diabetes Federation (IDF) (2017) IDF Diabetes Atlas 8th edn. IDF. http://www.idf.org/diabetesatlas

Parving HH, Lewis JB, Ravid M, Remuzzi G, Hunsicker LG (2006) Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int 69(11):2057–2063CrossRefPubMed

Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR (2006) Risk factors for renal dysfunction in type 2 diabetes: U.K. prospective diabetes study 74. Diabetes 55(6):1832–1839CrossRefPubMed

Burrows NR, Hora I, Geiss LS, Gregg EW, Albright A (2017) Incidence of end-stage renal disease attributed to diabetes among persons with Diagnosed diabetes—United States and Puerto Rico, 2000–2014. MMWR Morb Mortal Wkly Rep 66(43):1165–1170CrossRefPubMedPubMedCentral

Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J et al (2014) Diabetic kidney disease: a report from an ADA consensus conference. Diabetes Care 37(10):2864–2883CrossRef

DeFronzo RA, Hompesch M, Kasichayanula S, Liu X, Hong Y, Pfister M et al (2013) Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care 36(10):3169–3176CrossRefPubMedPubMedCentral

Tikkanen I, Narko K, Zeller C, Green A, Salsali A, Broedl UC et al (2015) Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care 38(3):420–428CrossRefPubMed

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373(22):2117–2128CrossRef

Gembardt F, Bartaun C, Jarzebska N, Mayoux E, Todorov VT, Hohenstein B et al (2014) The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. Am J Physiol Renal Physiol 307(3):F317–F325CrossRefPubMed

10.

Heerspink HJ, Desai M, Jardine M, Balis D, Meininger G, Perkovic V (2017) Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol 28(1):368–375CrossRefPubMed

11.

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M et al (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375(4):323–334CrossRef

12.

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377(7):644–657CrossRef

13.

Liu XY, Zhang N, Chen R, Zhao JG, Yu P (2015) Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years. J Diabetes Complicat 29(8):1295–1303CrossRefPubMed

14.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700CrossRefPubMedPubMedCentral

15.

Ji L, Ma J, Li H, Mansfield TA, T’Joen CL, Iqbal N et al (2014) Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther 36(1):84.e109–100.e109CrossRef

16.

Bailey CJ, Morales Villegas EC, Woo V, Tang W, Ptaszynska A, List JF (2015) Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. Diabet Med 32(4):531–541CrossRefPubMed

17.

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):962–971CrossRefPubMed

18.

Wilding JP, Norwood P, T’Joen C, Bastien A, List JF, Fiedorek FT (2009) A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care 32(9):1656–1662CrossRefPubMedPubMedCentral

19.

Strojek K, Yoon KH, Hruba V, Sugg J, Langkilde AM, Parikh S (2014) Dapagliflozin added to glimepiride in patients with type 2 diabetes mellitus sustains glycemic control and weight loss over 48 weeks: a randomized, double-blind, parallel-group, placebo-controlled trial. Diabetes Ther 5(1):267–283CrossRefPubMedPubMedCentral

20.

Yang W, Ma J, Li Y, Li Y, Zhou Z, Kim JH et al (2018) Dapagliflozin as add-on therapy in Asian patients with type 2 diabetes inadequately controlled on insulin with or without oral antihyperglycemic drugs: a randomized controlled trial. J Diabetes 10(7):589–599CrossRefPubMed

21.

Bolinder J, Ljunggren O, Kullberg J, Johansson L, Wilding J, Langkilde AM et al (2012) Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97(3):1020–1031CrossRefPubMed

22.

Araki E, Onishi Y, Asano M, Kim H, Yajima T (2017) Efficacy and safety of dapagliflozin over 1 year as add-on to insulin therapy in Japanese patients with type 2 diabetes: the DAISY (Dapagliflozin Added to patients under InSulin therapY) trial. Diabetes Obes Metab 19(4):562–570CrossRefPubMed

23.

Schumm-Draeger PM, Burgess L, Koranyi L, Hruba V, Hamer-Maansson JE, de Bruin TW (2015) Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial. Diabetes Obes Metab 17(1):42–51CrossRefPubMed

24.

Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M et al (2011) Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 34(9):2015–2022CrossRefPubMedPubMedCentral

25.

Wilding JP, Woo V, Rohwedder K, Sugg J, Parikh S (2014) Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab 16(2):124–136CrossRefPubMed

26.

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):853–862CrossRefPubMed

27.

Rosenstock J, Chuck L, Gonzalez-Ortiz M, Merton K, Craig J, Capuano G et al (2016) Initial combination therapy with canagliflozin plus metformin versus each component as monotherapy for drug-naive type 2 diabetes. Diabetes Care 39(3):353–362CrossRefPubMed

28.

Inagaki N, Kondo K, Yoshinari T, Takahashi N, Susuta Y, Kuki H (2014) Efficacy and safety of canagliflozin rnonotherapy in Japanese patients with type 2 diabetes inadequately controlled with diet and exercise: a 24-week, randomized, double-blind, placebo-controlled, phase III study. Expert Opin Pharmacother 15(11):1501–1515CrossRefPubMed

29.

Stenlof K, Cefalu WT, Kim KA, Jodar E, Alba M, Edwards R et al (2014) Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATA-M study. Curr Med Res Opin 30(2):163–175CrossRefPubMed

30.

Bode B, Stenlof K, Harris S, Sullivan D, Fung A, Usiskin K et al (2015) Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55–80 years with type 2 diabetes. Diabetes Obes Metab 17(3):294–303CrossRefPubMed

31.

Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J et al (2013) Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care 36(9):2508–2515CrossRefPubMedPubMedCentral

32.

Sha S, Polidori D, Heise T, Natarajan J, Farrell K, Wang SS et al (2014) Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Diabetes Obes Metab 16(11):1087–1095CrossRefPubMed

33.

Qiu R, Capuano G, Meininger G (2014) Efficacy and safety of twice-daily treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, added on to metformin monotherapy in patients with type 2 diabetes mellitus. J Clin Transl Endocrinol 1(2):54–60PubMedPubMedCentral

34.

Ji L, Han P, Liu Y, Yang G, Dieu Van NK, Vijapurkar U et al (2015) Canagliflozin in Asian patients with type 2 diabetes on metformin alone or metformin in combination with sulphonylurea. Diabetes Obes Metab 17(1):23–31CrossRefPubMed

35.

Lavalle-Gonzalez FJ, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W et al (2013) Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 56(12):2582–2592CrossRefPubMedPubMedCentral

36.

Wilding JP, Charpentier G, Hollander P, Gonzalez-Galvez G, Mathieu C, Vercruysse F et al (2013) Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract 67(12):1267–1282CrossRefPubMedPubMedCentral

37.

Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J et al (2013) Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382(9896):941–950CrossRefPubMed

38.

Forst T, Guthrie R, Goldenberg R, Yee J, Vijapurkar U, Meininger G et al (2014) Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab 16(5):467–477CrossRefPubMedPubMedCentral

39.

Yale JF, Bakris G, Cariou B, Yue D, David-Neto E, Xi L et al (2013) Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 15(5):463–473CrossRefPubMedPubMedCentral

40.

Rodbard HW, Seufert J, Aggarwal N, Cao A, Fung A, Pfeifer M et al (2016) Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes mellitus inadequately controlled on metformin and sitagliptin. Diabetes Obes Metab 18(8):812–819CrossRefPubMedPubMedCentral

41.

Kadowaki T, Haneda M, Inagaki N, Terauchi Y, Taniguchi A, Koiwai K et al (2014) Empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, 12-week, double-blind, placebo-controlled, phase II trial. Adv Ther 31(6):621–638CrossRefPubMed

42.

Lewin A, DeFronzo RA, Patel S, Liu D, Kaste R, Woerle HJ et al (2015) Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care 38(3):394–402CrossRefPubMed

43.

Roden M, Merker L, Christiansen AV, Roux F, Salsali A, Kim G et al (2015) Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug-naive patients with type 2 diabetes: a double-blind extension of a Phase III randomized controlled trial. Cardiovasc Diabetol 14:154CrossRefPubMedPubMedCentral

44.

Hadjadj S, Rosenstock J, Meinicke T, Woerle HJ. Initial combination of empagliflozin and metformin in patients with type 2 diabetes. 2016,39(10):1718–1728

45.

Nishimura R, Tanaka Y, Koiwai K, Inoue K, Hach T, Salsali A et al (2015) Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study. Cardiovasc Diabetol 14:11CrossRefPubMedPubMedCentral

46.

DeFronzo RA, Lewin A, Patel S, Liu D, Kaste R, Woerle HJ et al (2015) Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care 38(3):384–393CrossRefPubMed

47.

Ross S, Thamer C, Cescutti J, Meinicke T, Woerle HJ, Broedl UC (2015) Efficacy and safety of empagliflozin twice daily versus once daily in patients with type 2 diabetes inadequately controlled on metformin: a 16-week, randomized, placebo-controlled trial. Diabetes Obes Metab 17(7):699–702CrossRefPubMed

48.

Softeland E, Meier JJ, Vangen B, Toorawa R, Maldonado-Lutomirsky M, Broedl UC (2017) Empagliflozin as add-on therapy in patients with type 2 diabetes inadequately controlled with linagliptin and metformin: a 24-week randomized, double-blind, parallel-group trial. Diabetes Care 40(2):201–209CrossRefPubMed

49.

Haring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Broedl UC et al (2014) Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 37(6):1650–1659CrossRefPubMed

50.

Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle HJ (2015) Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 17(10):936–948CrossRefPubMedPubMedCentral

51.

Rosenstock J, Jelaska A, Frappin G, Salsali A, Kim G, Woerle HJ et al (2014) Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care 37(7):1815–1823CrossRefPubMed

52.

Kovacs CS, Seshiah V, Merker L, Christiansen AV, Roux F, Salsali A et al (2015) Empagliflozin as add-on therapy to pioglitazone with or without metformin in patients with type 2 diabetes mellitus. Clin Ther 37(8):1773–1788.e1771CrossRefPubMed

53.

Merker L, Haring HU, Christiansen AV, Roux F, Salsali A, Kim G et al (2015) Empagliflozin as add-on to metformin in people with Type 2 diabetes. Diabet Med 32(12):1555–1567CrossRefPubMed

54.

Haering HU, Merker L, Christiansen AV, Roux F, Salsali A, Kim G et al (2015) Empagliflozin as add-on to metformin plus sulphonylurea in patients with type 2 diabetes. Diabetes Res Clin Pract 110(1):82–90CrossRefPubMed

55.

Barnett AH, Mithal A, Manassie J, Jones R, Rattunde H, Woerle HJ et al (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):369–384CrossRefPubMed

56.

Fonseca VA, Ferrannini E, Wilding JP, Wilpshaar W, Dhanjal P, Ball G et al (2013) Active- and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus. J Diabetes Complicat 27(3):268–273CrossRefPubMed

57.

Kashiwagi A, Kazuta K, Takinami Y, Yoshida S, Utsuno A, Nagase I (2015) Ipragliflozin improves glycemic control in Japanese patients with type 2 diabetes mellitus: the BRIGHTEN study. Diabetol Int 6(1):8–18CrossRef

58.

Wilding JP, Ferrannini E, Fonseca VA, Wilpshaar W, Dhanjal P, Houzer A (2013) Efficacy and safety of ipragliflozin in patients with type 2 diabetes inadequately controlled on metformin: a dose-finding study. Diabetes Obes Metab 15(5):403–409CrossRefPubMed

59.

Lu CH, Min KW, Chuang LM, Kokubo S, Yoshida S, Cha BS (2016) Efficacy, safety, and tolerability of ipragliflozin in Asian patients with type 2 diabetes mellitus and inadequate glycemic control with metformin: results of a phase 3 randomized, placebo-controlled, double-blind, multicenter trial. J Diabetes Investig 7(3):366–373CrossRefPubMed

60.

Kashiwagi A, Akiyama N, Shiga T, Kazuta K, Utsuno A, Yoshida S et al (2015) Efficacy and safety of ipragliflozin as an add-on to a sulfonylurea in Japanese patients with inadequately controlled type 2 diabetes: results of the randomized, placebo-controlled, double-blind, phase III EMIT study. Diabetol Int 6(2):125–138CrossRef

61.

Kashiwagi A, Shiga T, Akiyama N, Kazuta K, Utsuno A, Yoshida S et al (2015) Efficacy and safety of ipragliflozin as an add-on to pioglitazone in Japanese patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study (the SPOTLIGHT study). Diabetol Int 6(2):104–116CrossRef

62.

Kashiwagi A, Takahashi H, Ishikawa H, Yoshida S, Kazuta K, Utsuno A et al (2015) A randomized, double-blind, placebo-controlled study on long-term efficacy and safety of ipragliflozin treatment in patients with type 2 diabetes mellitus and renal impairment: results of the long-term ASP1941 safety evaluation in patients with type 2 diabetes with renal impairment (LANTERN) study. Diabetes Obes Metab 17(2):152–160CrossRefPubMedPubMedCentral

63.

Kaku K, Watada H, Iwamoto Y, Utsunomiya K, Terauchi Y, Tobe K et al (2014) Efficacy and safety of monotherapy with the novel sodium/glucose cotransporter-2 inhibitor tofogliflozin in Japanese patients with type 2 diabetes mellitus: a combined Phase 2 and 3 randomized, placebo-controlled, double-blind, parallel-group comparative study. Cardiovasc Diabetol 13:65CrossRefPubMedPubMedCentral

64.

Terra SG, Focht K, Davies M (2017) Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone. Diabetes Obes Metab 19(5):721–728CrossRefPubMed

65.

Xu L, Li Y, Lang J, Xia P, Zhao X, Wang L et al (2017) Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis. PeerJ 5:e3405CrossRefPubMedPubMedCentral

66.

Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J (2005) Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 54(12):3427–3434CrossRefPubMed

67.

Tabatabai NM, Sharma M, Blumenthal SS, Petering DH (2009) Enhanced expressions of sodium-glucose cotransporters in the kidneys of diabetic Zucker rats. Diabetes Res Clin Pract 83(1):e27–e30CrossRefPubMed

68.

Freitas HS, Anhe GF, Melo KF, Okamoto MM, Oliveira-Souza M, Bordin S et al (2008) Na(+)-glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1alpha expression and activity. Endocrinology 149(2):717–724CrossRefPubMed

69.

Chichger H, Cleasby ME, Srai SK, Unwin RJ, Debnam ES, Marks J (2016) Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane. Exp Physiol 101(6):731–742CrossRefPubMed

70.

Hannedouche TP, Delgado AG, Gnionsahe DA, Boitard C, Lacour B, Grunfeld JP (1990) Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes. Kidney Int 37(4):1126–1133CrossRefPubMed

71.

Vallon V, Richter K, Blantz RC, Thomson S, Osswald H (1999) Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J Am Soc Nephrol 10(12):2569–2576PubMed

72.

Brenner BM (1983) Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 23(4):647–655CrossRefPubMed

73.

Vallon V, Rose M, Gerasimova M, Satriano J, Platt KA, Koepsell H et al (2013) Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. Am J Physiol Renal Physiol 304(2):F156–F167CrossRefPubMed

74.

Yale JF, Bakris G, Cariou B, Nieto J, David-Neto E, Yue D et al (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):1016–1027CrossRefPubMed

75.

Rajasekeran H, Reich HN, Hladunewich MA, Cattran D, Lovshin JA, Lytvyn Y et al (2018) Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study. Am J Physiol Renal Physiol 314(3):F412–Ff422CrossRefPubMed

76.

Macha S, Mattheus M, Halabi A, Pinnetti S, Woerle HJ, Broedl UC (2014) Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes Obes Metab 16(3):215–222CrossRefPubMed

77.

Vallon V, Gerasimova M, Rose MA, Masuda T, Satriano J, Mayoux E et al (2014) SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol 306(2):F194–F204CrossRefPubMed

78.

Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S et al (2016) The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia 59(9):1860–1870CrossRefPubMed

79.

Gangadharan Komala M, Gross S, Mudaliar H, Huang C, Pegg K, Mather A et al (2014) Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice. PLoS ONE 9(11):e108994CrossRefPubMedPubMedCentral

80.

Iemitsu K, Iizuka T, Takihata M, Takai M, Nakajima S, Minami N et al (2016) Factors influencing changes in hemoglobin A1c and body weight during treatment of type 2 diabetes with ipragliflozin: interim analysis of the ASSIGN-K study. J Clin Med Res 8(5):373–378CrossRefPubMedPubMedCentral

81.

Perkovic V, Heerspink HL, Chalmers J, Woodward M, Jun M, Li Q et al (2013) Intensive glucose control improves kidney outcomes in patients with type 2 diabetes. Kidney Int 83(3):517–523CrossRefPubMed

82.

Kramer H, Reboussin D, Bertoni AG, Marcovina S, Lipkin E, Greenway FL III, et al (2009) Obesity and albuminuria among adults with type 2 diabetes: the Look AHEAD (action for health in diabetes) study. Diabetes Care 32(5):851–853CrossRefPubMedPubMedCentral

83.

Huang M, Matsushita K, Sang Y, Ballew SH, Astor BC, Coresh J (2015) Association of kidney function and albuminuria with prevalent and incident hypertension: the atherosclerosis risk in communities (ARIC) study. Am J Kidney Dis 65(1):58–66CrossRefPubMed

84.

Abdel-Wahab AF, Bamagous GA, Al-Harizy RM, ElSawy NA, Shahzad N, Ibrahim IA et al (2018) Renal protective effect of SGLT2 inhibitor dapagliflozin alone and in combination with irbesartan in a rat model of diabetic nephropathy. Biomed Pharmacother 103:59–66CrossRefPubMed

85.

Petrykiv SI, Laverman GD, de Zeeuw D, Heerspink HJL (2017) The albuminuria-lowering response to dapagliflozin is variable and reproducible among individual patients. Diabetes Obes Metab 19(10):1363–1370CrossRefPubMed

86.

Petrykiv S, Laverman GD, de Zeeuw D, Heerspink HJL (2018) Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition? Diabetes Obes Metab 20(1):224–227CrossRefPubMed

87.

Sakai S, Kaku K, Seino Y, Inagaki N, Haneda M, Sasaki T et al (2016) Efficacy and safety of the SGLT2 inhibitor luseogliflozin in Japanese patients with type 2 diabetes mellitus stratified according to baseline body mass index: pooled analysis of data from 52-week phase III trials. Clin Ther 38(4):843.e849–862.e849CrossRef

Title: Effect of SGLT2 inhibitor on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Authors: Chaojie Feng
Minxiang Wu
Zhengyue Chen
Xiongwei Yu
Zhenyu Nie
Yu Zhao
Beiyan Bao
Publication date: 01-04-2019
Publisher: Springer Netherlands
Keywords: Sulfonylurea
Metformin
Empagliflozin
Albuminuria
Diabetes
Type 2 Diabetes
Published in: International Urology and Nephrology / Issue 4/2019
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI: https://doi.org/10.1007/s11255-019-02112-6

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Pentoxifylline for the prevention of contrast-induced nephropathy in diabetic patients undergoing angioplasty: a randomized controlled trial

Development of symptomatic lymphoceles after radical prostatectomy and pelvic lymph node dissection is independent of surgical approach: a single-center analysis

Defining a clinically significant struvite stone: a non-randomized retrospective study

How to estimate renal function in patients with liver disease: choosing the most suitable equation

A simple modified open peritoneal dialysis catheter insertion procedure reduces the need for secondary surgery

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

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