Preventing diabetic renal disease: the potential reno-protective effects of SGLT2 inhibitors

Authors

  • Giuseppe Maltese Cardiovascular Division, King’s College London, London, UK
  • Ahmad Abou-Saleh Cardiovascular Division, King’s College London, London, UK
  • Luigi Gnudi Cardiovascular Division, King’s College London, London, UK
  • Janaka Karalliedde Cardiovascular Division, King’s College London, London, UK

DOI:

https://doi.org/10.15277/bjdvd.2015.030

Abstract

Diabetic renal disease is associated with increased cardiovascular risk and is one of the leading causes of end-stage renal disease worldwide. A combination of hyperglycaemia and hypertension drives the development and progression of diabetic renal disease, with glomerular hyperfiltration being an early manifestation of the disease process. Sodium- glucose linked transporter 2 (SGLT2) inhibitors represent a novel class of drugs that lower plasma glucose levels through the inhibition of renal proximal tubular glucose uptake and secondary glycosuria.

Clinical evidence that SGLT2 inhibitors attenuate glomerular hyperfiltration is complemented by animal data suggesting that these agents can prevent progression of diabetic renal disease. In clinical studies involving patients with type 1 and type 2 diabetes, SGLT2 inhibition reduces glomerular hyperfiltration and appears (albeit in post-hoc and pooled analyses) to reduce urinary albumin excretion. The longer term potential reno-protective effects of this class of drugs are currently under evaluation in large randomised clinical trials.

References

Karalliedde J and Viberti GC. Diabetic Nephropathy. 2nd edition. Davies M AS, editor. Oxford: Oxford University Press 2011.

Karalliedde J and Viberti GC. Proteinuria in diabetes: bystander or pathway to cardiorenal disease? JASN 2010;21:2020-7. http://dx.doi.org/10.1681/ASN.2010030250

Viberti GC, Hill RD, Jarrett RJ et al. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982;1:1430-2. http://dx.doi.org/10.1016/S0140-6736(82)92450-3

Rosenwasser RF, Sultan S, Sutton D et al. SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes Metab Syndr Obes 2013; 6:453-67. http://dx.doi.org/10.2147/DMSO.S34416

Musso G, Gambino R, Cassader M et al. A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med 2012;44:375-93. http://dx.doi.org/10.3109/07853890.2011.560181

Vasilakou D, Karagiannis T, Athanasiadou E et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2013;159:262-74. http://dx.doi.org/10.7326/0003-4819-159-4-201308200-00007

Jerums G, Premaratne E, Panagiotopoulos S et al. The clinical significance of hyperfiltration in diabetes. Diabetologia 2010;53:2093-104. http://dx.doi.org/10.1007/s00125-010-1794-9

Magee GM, Bilous RW, Cardwell CR et al. Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia 2009;52:691-7. http://dx.doi.org/10.1007/s00125-009-1268-0

Sasson AN, Cherney DZ. Renal hyperfiltration related to diabetes mellitus and obesity in human disease. World J Diabetes 2012;3:1-6. http://dx.doi.org/10.4239/wjd.v3.i1.1

Melsom T, Mathisen UD, Ingebretsen OC et al. Impaired fasting glucose is associated with renal hyperfiltration in the general population. Diabetes Care 2011;34:1546-51. http://dx.doi.org/10.2337/dc11-0235

ter Maaten JC, Bakker SJ, Serne EH et al. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects. Nepron Dial Transplant 1999;14:2357-63. http://dx.doi.org/10.1093/ndt/14.10.2357

Oterdoom LH, de Vries AP, Gansevoort RT et al. Fasting insulin modifies the relation between age and renal function. Nepron Dial Transplant 2007;22:1587-92. http://dx.doi.org/10.1093/ndt/gfm037

Wright EM. Renal Na(+)-glucose cotransporters. Am J Physiol Renal Physiol 2001;280:F10-8.

Vallon V, Platt KA, Cunard R et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol 2011;22:104-12. http://dx.doi.org/10.1681/ASN.2010030246

Mather A, Pollock C. Renal glucose transporters: novel targets for hyperglycemia management. Nature Rev Nephrol 2010;6:307-11. http://dx.doi.org/10.1038/nrneph.2010.38

Cherney DZ, Perkins BA, Soleymanlou N et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 2014;129:587-97. http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005081

Vallon V, Gerasimova M, Rose MA et al. 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 2014;306:F194-204. http://dx.doi.org/10.1152/ajprenal.00520.2013

Ly JP, Onay T, Sison K et al. The Sweet Pee model for Sglt2 mutation. J Am Soc Nephrol 2011;22:113-23. http://dx.doi.org/10.1681/ASN.2010080888

List JF, Woo V, Morales E et al. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009;32:650-7. http://dx.doi.org/10.2337/dc08-1863

Wilding JP, Woo V, Soler NG et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012;156:405-15. http://dx.doi.org/10.7326/0003-4819-156-6-201203200-00003

Cefalu WT, Leiter LA, Yoon KH et al. 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 2013;382:941-50. http://dx.doi.org/10.1016/S0140-6736(13)60683-2

Kohan DE, Fioretto P, Tang W et al. 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;85:962-71. http://dx.doi.org/10.1038/ki.2013.356

Yale JF, Bakris G, Cariou B et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2013;15:463-73. http://dx.doi.org/10.1111/dom.12090

Lambers Heerspink HJ, de Zeeuw D, Wie L et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab 2013;15:853-62. http://dx.doi.org/10.1111/dom.12127

Downloads

Published

2015-09-01

Issue

Vol. 15 No. 3 (2015)

Section

Reviews

License

Publish & Transfer of Copyright Agreement
For the mutual benefit and protection of the Author and the Journal Owner/Publisher it is necessary that the Author provides formal written Consent to Publish and Transfer of Copyright before publication of the Work.

Most read articles by the same author(s)