SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects

Carlo Garofalo, Silvio Borrelli, Maria Elena Liberti, Michele Andreucci, Giuseppe Conte, Roberto Minutolo, Michele Provenzano, Luca De Nicola, Carlo Garofalo, Silvio Borrelli, Maria Elena Liberti, Michele Andreucci, Giuseppe Conte, Roberto Minutolo, Michele Provenzano, Luca De Nicola

Abstract

The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that is, the inhibitors of renin-angiotensin system. Nephroprotection in DKD therefore remains a major unmet need. Three recent trials testing effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) have produced great expectations on this therapy by consistently evidencing positive effects on hyperglycemia control, and more importantly, on the cardiovascular outcome of type 2 diabetes mellitus. Notably, these trials also disclosed nephroprotective effects when renal outcomes (glomerular filtration rate and albuminuria) were analyzed as secondary endpoints. On the other hand, the use of SGLT2-i can be potentially associated with some adverse effects. However, the balance between positive and negative effects is in favor of the former. The recent results of Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation Study and of other trials specifically testing these drugs in the population with chronic kidney disease, either diabetic or non-diabetic, do contribute to further improving our knowledge of these antihyperglycemic drugs. Here, we review the current state of the art of SGLT2-i by addressing all aspects of therapy, from the pathophysiological basis to clinical effectiveness.

Keywords: GFR; SGLT-2 inhibitors; albuminuria; chronic kidney disease; diabetes; end stage renal disease; survival.

Conflict of interest statement

L.D.N. received fee for scientific consultation/lecture from Astrazeneca and Janssen; the other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Intrarenal mechanisms underlying Diabetic Kidney Disease. Hyperglycemia increases Angiotensin II synthesis at glomerular and renal proximal tubular level with consequent proximal tubule growth (hyperplasia and hypertrophy). Hyperglycemia and tubular growth cause enhanced expression of SGLT2s with consequent higher proximal tubular reabsorption of glucose and Na. The dependent reduction of distal Na delivery to macula densa determines the deactivation of tubulo-glomerular feedback, which, in turn, allows single-nephron GFR to increase (diabetic hyperfiltration). GFR increase, abnormal albuminuria and extracellular volume expansion with dependent systemic hypertension lead to progressive diabetic kidney disease. Prox, proximal; Reab, reabsorption; RE, efferent arteriole resistance; RA, afferent arteriole resistance; MD, macula densa; TGF, tubulo-glomerular feedback; EC, extracellular volume; BP, blood pressure; GFR, glomerular filtration rate; CKD, Chronic Kidney Disease.
Figure 2
Figure 2
Insulin-sparing and nephroprotective antidiabetic therapy in diabetic kidney disease (eGFR > 30 mL/min/1.73 m2). eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease; DPP4i, dipeptidyl peptidase 4 inhibitors; SGLT2-i, sodium glucose transporter 2 inhibitors; GLP1-RA, GLP1 receptor agonists. HbA1C target should be around 7%, more or less stringent according to patient features [77].

References

    1. Xie Y., Bowe B., Mokdad A.H., Xian H., Yan Y., Li T., Maddukuri G., Tsai C.Y., Floyd T., Al-Aly Z. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int. 2018;94:567–581. doi: 10.1016/j.kint.2018.04.011.
    1. NCD Risk Factor Collaboration (NCD-RisC) Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387:1513–1530. doi: 10.1016/S0140-6736(16)00618-8.
    1. Gregg E.W., Li Y., Wang J., Burrows N.R., Ali M.K., Rolka D., Williams D.E., Geiss L. Changes in diabetes-related complications in the United States, 1990–2010. N. Engl. J. Med. 2014;370:1514–1523. doi: 10.1056/NEJMoa1310799.
    1. Ali M.K., Bullard K.M., Saydah S., Imperatore G., Gregg E.W. Cardiovascular and renal burdens of prediabetes in the USA: Analysis of data from serial cross-sectional surveys, 1988–2014. Lancet Diabetes Endocrinol. 2018;6:392–403. doi: 10.1016/S2213-8587(18)30027-5.
    1. Brenner B.M., Cooper M.E., de Zeeuw D., Keane W.F., Mitch W.E., Parving H.H., Remuzzi G., Snapinn S.M., Zhang Z., Shahinfar S., et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl. J. Med. 2001;345:861–869. doi: 10.1056/NEJMoa011161.
    1. Lewis E.J., Hunsicker L.G., Clarke W.R., Berl T., Pohl M.A., Lewis J.B., Ritz E., Atkins R.C., Rohde R., Raz I., et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N. Engl. J. Med. 2001;345:851–860. doi: 10.1056/NEJMoa011303.
    1. Levin A., Tonelli M., Bonventre J., Coresh J., Donner J.A., Fogo A.B., Fox C.S., Gansevoort R.T., Heerspink H.J.L., Jardine M., et al. Global kidney health 2017 and beyond: A roadmap for closing gaps in care, research, and policy. Lancet. 2017;390:1888–1917. doi: 10.1016/S0140-6736(17)30788-2.
    1. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 2008;359:1577–1589. doi: 10.1056/NEJMoa0806470.
    1. Li Vecchi M., Fuiano G., Francesco M., Mancuso D., Faga T., Sponton A., Provenzano R., Andreucci M., Tozzo C. Prevalence and severity of anaemia in patients with type 2 diabetic nephropathy and different degrees of chronic renal insufficiency. Nephron Clin. Pract. 2007;105:c62–c67. doi: 10.1159/000097600.
    1. Rao Kondapally Seshasai S., Kaptoge S., Thompson A., Di Angelantonio E., Gao P., Sarwar N., Whincup P.H., Mukamal K.J., Gillum R.F., Holme I., et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N. Engl. J. Med. 2011;364:829–841.
    1. Minutolo R., Gabbai F.B., Provenzano M., Chiodini P., Borrelli S., Garofalo C., Sasso F.C., Santoro D., Bellizzi V., Conte G., et al. Cardiorenal prognosis by residual proteinuria level in diabetic chronic kidney disease: Pooled analysis of four cohort studies. Nephrol. Dial. Transpl. 2018;33:1942–1949. doi: 10.1093/ndt/gfy032.
    1. Afkarian M., Sachs M.C., Kestenbaum B., Hirsch I.B., Tuttle K.R., Himmelfarb J., de Boer I.H. Kidney disease and increased mortality risk in type 2 diabetes. J. Am. Soc. Nephrol. 2013;24:302–308. doi: 10.1681/ASN.2012070718.
    1. O’Shaughnessy M.M., Montez-Rath M.E., Lafayette R.A., Winkelmayer W.C. Patient characteristics and outcomes by GN subtype in ESRD. Clin. J. Am. Soc. Nephrol. 2015;10:1170–1178. doi: 10.2215/CJN.11261114.
    1. De Nicola L., Gabbai F.B., Liberti M.E., Sagliocca A., Conte G., Minutolo R. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: Targeting the renal tubule in diabetes. Am. J. Kidney Dis. 2014;64:16–24. doi: 10.1053/j.ajkd.2014.02.010.
    1. Wright E.M., Hirayama B.A., Loo D.F. Active sugar transport in health and disease. J. Intern. Med. 2007;261:32–43. doi: 10.1111/j.1365-2796.2006.01746.x.
    1. Gerich J.E. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications. Diabetes Med. 2010;27:136–142. doi: 10.1111/j.1464-5491.2009.02894.x.
    1. Coady M.J., Wallendorff B., Lapointe J.Y. Characterization of the transport activity of SGLT2/MAP17, the renal low-affinity Na(+)-glucose cotransporter. Am. J. Physiol. Renal. Physiol. 2017;313:F467–F474. doi: 10.1152/ajprenal.00628.2016.
    1. Ruhnau B., Faber O.K., Borch-Johnsen K., Thorsteinsson B. Renal threshold for glucose in non-insulin-dependent diabetic patients. Diabetes Res. Clin. Pract. 1997;36:27–33. doi: 10.1016/S0168-8227(97)01389-2.
    1. Alsahli M., Gerich J.E. Renal glucose metabolism in normal physiological conditions and in diabetes. Diabetes Res. Clin. Pract. 2017;133:1–9. doi: 10.1016/j.diabres.2017.07.033.
    1. Freitas H.S., Anhê G.F., Melo K.F., Okamoto M.M., Oliveira-Souza M., Bordin S., Machado U.F. 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. 2008;149:717–724. doi: 10.1210/en.2007-1088.
    1. Gallo L.A., Ward M.S., Fotheringham A.K., Zhuang A., Borg D.J., Flemming N.B., Harvie B.M., Kinneally T.L., Yeh S.M., McCarthy D.A., et al. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice. Sci. Rep. 2016;6:26428. doi: 10.1038/srep26428.
    1. Rahmoune H., Thompson P.W., Ward J.M., Smith C.D., Hong G., Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes. 2005;54:3427–3434. doi: 10.2337/diabetes.54.12.3427.
    1. Norton L., Shannon C.E., Fourcaudot M., Hu C., Wang N., Ren W., Song J., Abdul-Ghani M., DeFronzo R.A., Ren J., et al. Sodium-glucose co-transporter (SGLT) and glucose transporter (GLUT) expression in the kidney of type 2 diabetic subjects. Diabetes Obes. Metab. 2017;19:1322–1326. doi: 10.1111/dom.13003.
    1. DeFronzo R.A., Hompesch M., Kasichayanula S., Liu X., Hong Y., Pfister M., Morrow L.A., Leslie B.R., Boulton D.W., Ching A., et al. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013;36:3169–3176. doi: 10.2337/dc13-0387.
    1. Premaratne E., Verma S., Ekinci E.I., Theverkalam G., Jerums G., MacIsaac R.J. The impact of hyperfiltration on the diabetic kidney. Diabetes Metab. 2015;41:5–17. doi: 10.1016/j.diabet.2014.10.003.
    1. Tuttle K.R. Back to the Future: Glomerular Hyperfiltration and the Diabetic Kidney. Diabetes. 2017;66:14–16. doi: 10.2337/dbi16-0056.
    1. De Nicola L., Conte G., Minutolo R. Prediabetes as a Precursor to Diabetic Kidney Disease. Am. J. Kidney Dis. 2016;67:817–819. doi: 10.1053/j.ajkd.2016.03.411.
    1. Heerspink H.J., Perkins B.A., Fitchett D.H., Husain M., Cherney D.Z. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Circulation. 2016;134:752–772. doi: 10.1161/CIRCULATIONAHA.116.021887.
    1. Ishibashi Y., Matsui T., Yamagishi S. Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation. Horm. Metab. Res. 2016;48:191–195. doi: 10.1055/s-0035-1555791.
    1. Ojima A., Matsui T., Nishino Y., Nakamura N., Yamagishi S. Empagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti-Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly by Suppressing AGEs-Receptor Axis. Horm. Metab. Res. 2015;47:686–692. doi: 10.1055/s-0034-1395609.
    1. O’Brien T.P., Jenkins E.C., Estes S.K., Castaneda A.V., Ueta K., Farmer T.D., Puglisi A.E., Swift L.L., Printz R.L., Shiota M. Correcting Postprandial Hyperglycemia in Zucker Diabetic Fatty Rats with an SGLT2 Inhibitor Restores Glucose Effectiveness in the Liver and Reduces Insulin Resistance in Skeletal Muscle. Diabetes. 2017;66:1172–1184. doi: 10.2337/db16-1410.
    1. Ferrannini E., Muscelli E., Frascerra S., Baldi S., Mari A., Heise T., Broedl U.C., Woerle H.J. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J. Clin. Investig. 2014;124:499–508. doi: 10.1172/JCI72227.
    1. Merovci A., Solis-Herrera C., Daniele G., Eldor R., Fiorentino T.V., Tripathy D., Xiong J., Perez Z., Norton L., Abdul-Ghani M.A., et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J. Clin. Investig. 2014;124:509–514. doi: 10.1172/JCI70704.
    1. Koike Y., Shirabe S.I., Maeda H., Yoshimoto A., Arai K., Kumakura A., Hirao K., Terauchi Y. Effect of canagliflozin on the overall clinical state including insulin resistance in Japanese patients with type 2 diabetes mellitus. Diabetes Res. Clin. Pract. 2019;149:140–146. doi: 10.1016/j.diabres.2019.01.029.
    1. Zinman B., Wanner C., Lachin J.M., Fitchett D., Bluhmki E., Hantel S., Mattheus M., Devins T., Johansen O.E., Woerle H.J., et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N. Engl. J. Med. 2015;373:2117–2128. doi: 10.1056/NEJMoa1504720.
    1. Wanner C., Lachin J.M., Inzucchi S.E., Fitchett D., Mattheus M., George J., Woerle H.J., Broedl U.C., von Eynatten M., Zinman B., et al. Empagliflozin and Clinical Outcomes in Patients with Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease. Circulation. 2018;137:119–129. doi: 10.1161/CIRCULATIONAHA.117.028268.
    1. Wanner C., Inzucchi S.E., Lachin J.M., Fitchett D., von Eynatten M., Mattheus M., Johansen O.E., Woerle H.J., Broedl U.C., Zinman B., et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N. Engl. J. Med. 2016;375:323–334. doi: 10.1056/NEJMoa1515920.
    1. Neal B., Perkovic V., Mahaffey K.W., de Zeeuw D., Fulcher G., Erondu N., Shaw W., Law G., Desai M., Matthews D.R., et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N. Engl. J. Med. 2017;377:644–657. doi: 10.1056/NEJMoa1611925.
    1. Neuen B.L., Ohkuma T., Neal B., Matthews D.R., de Zeeuw D., Mahaffey K.W., Fulcher G., Desai M., Li Q., Deng H., et al. Cardiovascular and Renal Outcomes with Canagliflozin According to Baseline Kidney Function. Circulation. 2018;138:1537–1550. doi: 10.1161/CIRCULATIONAHA.118.035901.
    1. Wiviott S.D., Raz I., Bonaca M.P., Mosenzon O., Kato E.T., Cahn A., Silverman M.G., Zelniker T.A., Kuder J.F., Murphy S.A., et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N. Engl. J. Med. 2019;380:347–357. doi: 10.1056/NEJMoa1812389.
    1. Petrykiv S.I., Laverman G.D., de Zeeuw D., Heerspink H.J.L. The albuminuria-lowering response to dapagliflozin is variable and reproducible among individual patients. Diabetes Obes. Metab. 2017;19:1363–1370. doi: 10.1111/dom.12936.
    1. Kohan D.E., Fioretto P., Tang W., List J.F. 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;85:962–971. doi: 10.1038/ki.2013.356.
    1. Seidu S., Kunutsor S.K., Cos X., Gillani S., Khunti K., Primary Care Diabetes Europe SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis. Prim. Care Diabetes. 2018;12:265–283. doi: 10.1016/j.pcd.2018.02.001.
    1. Heerspink H.J., Desai M., Jardine M., Balis D., Meininger G., Perkovic V. Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects. J. Am. Soc. Nephrol. 2017;28:368–375. doi: 10.1681/ASN.2016030278.
    1. Perkovic V., Jardine M.J., Neal B., Bompoint S., Heerspink H.H.L., Charytan D.M., Edwards R., Agarwal R., Bakris G., Bull S., et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N. Engl. J. Med. 2019 doi: 10.1056/NEJMoa1811744.
    1. Aeddula N.R., Cheungpasitporn W., Thongprayoon C., Pathireddy S. Epicardial Adipose Tissue and Renal Disease. J. Clin. Med. 2019;8:299. doi: 10.3390/jcm8030299.
    1. Bouchi R., Terashima M., Sasahara Y., Asakawa M., Fukuda T., Takeuchi T., Nakano Y., Murakami M., Minami I., Izumiyama H., et al. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: A pilot study. Cardiovasc. Diabetol. 2017;16:32. doi: 10.1186/s12933-017-0516-8.
    1. Fukuda T., Bouchi R., Terashima M., Sasahara Y., Asakawa M., Takeuchi T., Nakano Y., Murakami M., Minami I., Izumiyama H., et al. Ipragliflozin Reduces Epicardial Fat Accumulation in Non-Obese Type 2 Diabetic Patients with Visceral Obesity: A Pilot Study. Diabetes. 2017;8:851–861. doi: 10.1007/s13300-017-0279-y.
    1. Sato T., Aizawa Y., Yuasa S., Kishi S., Fuse K., Fujita S., Ikeda Y., Kitazawa H., Takahashi M., Sato M., et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc. Diabetol. 2018;17:6. doi: 10.1186/s12933-017-0658-8.
    1. Yagi S., Hirata Y., Ise T., Kusunose K., Yamada H., Fukuda D., Salim H.M., Maimaituxun G., Nishio S., Takagawa Y., et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol. Metab. Syndr. 2017;9:78. doi: 10.1186/s13098-017-0275-4.
    1. Singh M., Kumar A. Risks Associated with SGLT2 Inhibitors: An Overview. Curr. Drug Saf. 2018;13:84–91. doi: 10.2174/1574886313666180226103408.
    1. Dave C.V., Schneeweiss S., Patorno E. Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors. Diabetes Obes. Metab. 2019;21:434–438. doi: 10.1111/dom.13531.
    1. Vasilakou D., Karagiannis T., Athanasiadou E., Mainou M., Liakos A., Bekiari E., Sarigianni M., Matthews D.R., Tsapas A. Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann. Intern. Med. 2013;159:262–274. doi: 10.7326/0003-4819-159-4-201308200-00007.
    1. Zaccardi F., Webb D., Htike Z., Youssef D., Khunti K., Davies M. 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;18:783–794. doi: 10.1111/dom.12670.
    1. Wu J.H., Foote C., Blomster J., Toyama T., Perkovic V., Sundström J., Neal B. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: A systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4:411–419. doi: 10.1016/S2213-8587(16)00052-8.
    1. Li D., Wang T., Shen S., Fang Z., Dong Y., Tang H. 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. 2017;19:348–355. doi: 10.1111/dom.12825.
    1. Inzucchi S.E., Iliev H., Pfarr E., Zinman B. Empagliflozin and assessment of lower-limb amputations in the EMPA-REG outcome trial. Diabetes Care. 2018;41:e4–e5. doi: 10.2337/dc17-1551.
    1. Chang H.Y., Singh S., Mansour O., Baksh S., Alexander G.C. Association Between Sodium-Glucose Cotransporter 2 Inhibitors and Lower Extremity Amputation Among Patients with Type 2 Diabetes. JAMA Intern. Med. 2018;178:1190–1198. doi: 10.1001/jamainternmed.2018.3034.
    1. Yuan Z., DeFalco F.J., Ryan P.B., Schuemie M.J., Stang P.E., Berlin J.A., Desai M., Rosenthal N. Risk of lower extremity amputations in people with type 2 diabetes mellitus treated with sodium-glucose co-transporter-2 inhibitors in the USA: A retrospective cohort study. Diabetes Obes. Metab. 2018;20:582–589. doi: 10.1111/dom.13115.
    1. Matthews D.R., Li Q., Perkovic V., Mahaffey K.W., de Zeeuw D., Fulcher G., Desai M., Hiatt W.R., Nehler M., Fabbrini E., et al. Effects of canagliflozin on amputation risk in type 2 diabetes: The CANVAS Program. Diabetologia. 2019 doi: 10.1007/s00125-019-4839-8.
    1. Fralick M., Kim S.C., Schneeweiss S., Kim D., Redelmeier D.A., Patorno E. Fracture Risk After Initiation of Use of Canagliflozin: A Cohort Study. Ann. Intern. Med. 2019 doi: 10.7326/M18-0567.
    1. Ueda P., Svanström H., Melbye M., Eliasson B., Svensson A.M., Franzén S., Gudbjörnsdottir S., Hveem K., Jonasson C., Pasternak B. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: Nationwide register based cohort study. BMJ. 2018;363:k4365. doi: 10.1136/bmj.k4365.
    1. Toulis K.A., Bilezikian J.P., Thomas G.N., Hanif W., Kotsa K., Thayakaran R., Keerthy D., Tahrani A.A., Nirantharakumar K. Initiation of dapagliflozin and treatment-emergent fractures. Diabetes Obes. Metab. 2018;20:1070–1074. doi: 10.1111/dom.13176.
    1. Das S.R., Everett B.M., Birtcher K.K., Brown J.M., Cefalu W.T., Januzzi J.L., Jr., Kalyani R.R., Kosiborod M., Magwire M.L., Morris P.B., et al. 2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J. Am. Coll. Cardiol. 2018;72:3200–3223.
    1. de Jong M.A., Petrykiv S.I., Laverman G.D., van Herwaarden A.E., de Zeeuw D., Bakker S.J.L., Heerspink H.J.L., de Borst M.H. Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis. Clin. J. Am. Soc. Nephrol. 2019;14:66–73. doi: 10.2215/CJN.04530418.
    1. Peters A.L., Buschur E.O., Buse J.B., Cohan P., Diner J.C., Hirsch I.B. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015;38:1687–1693. doi: 10.2337/dc15-0843.
    1. Keller U., Schnell H., Sonnenberg G.E., Gerber P.P., Stauffacher W. Role of glucagon in enhancing ketone body production in ketotic diabetic man. Diabetes. 1983;32:387–391. doi: 10.2337/diab.32.5.387.
    1. Hahn K., Ejaz A.A., Kanbay M., Lanaspa M.A., Johnson R.J. Acute kidney injury from SGLT2 inhibitors: Potential mechanisms. Nat. Rev. Nephrol. 2016;12:711–712. doi: 10.1038/nrneph.2016.159.
    1. Hahn K., Kanbay M., Lanaspa M.A., Johnson R.J., Ejaz A.A. Serum uric acid and acute kidney injury: A mini review. J. Adv. Res. 2017;8:529–536. doi: 10.1016/j.jare.2016.09.006.
    1. Andreucci M., Faga T., Serra R., De Sarro G., Michael A. Update on the renal toxicity of iodinated contrast drugs used in clinical medicine. Drug Healthc. Patient Saf. 2017;9:25–37. doi: 10.2147/DHPS.S122207.
    1. Rivosecchi R.M., Kellum J.A., Dasta J.F., Armahizer M.J., Bolesta S., Buckley M.S., Dzierba A.L., Frazee E.N., Johnson H.J., Kim C., et al. Drug Class Combination-Associated Acute Kidney Injury. Ann. Pharm. 2016;50:953–972. doi: 10.1177/1060028016657839.
    1. Gomez-Peralta F., Abreu C., Lecube A., Bellido D., Soto A., Morales C., Brito-Sanfiel M., Umpierrez G. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes. 2017;8:953–962. doi: 10.1007/s13300-017-0277-0. Erratum in Diabetes Ther.2017, 8, 963–965.
    1. Bersoff-Matcha S.J., Chamberlain C., Cao C., Kortepeter C., Chong W.H. Fournier Gangrene Associated with Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases. Ann. Intern. Med. 2019 doi: 10.7326/M19-0085.
    1. Iazzetta N., Garofalo C., Savino M., Sagliocca A., Santangelo S., Pacilio M., Liberti M.E., Camocardi A., Ambrosca C., Minutolo R., et al. Nephroprotection with saxagliptin. G. Ital. Nefrol. 2015;32:gin/32.6.11.
    1. Coppolino G., Leporini C., Rivoli L., Ursini F., di Paola E.D., Cernaro V., Arturi F., Bolignano D., Russo E., De Sarro G., et al. Exploring the effects of DPP-4 inhibitors on the kidney from the bench to clinical trials. Pharm. Res. 2018;129:274–294. doi: 10.1016/j.phrs.2017.12.001.
    1. DeFronzo R.A. Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes. Metab. 2017;19:1353–1362. doi: 10.1111/dom.12982.
    1. American Diabetes Association 6. Glycemic Targets: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl. 1):S61–S70. doi: 10.2337/dc19-S006.
    1. American Diabetes Association 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl. 1):S90–S102. doi: 10.2337/dc19-S009.

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