Sodium-glucose cotransporter 2 inhibition in type 1 diabetes: simultaneous glucose lowering and renal protection?

Can J Diabetes. 2014 Oct;38(5):356-63. doi: 10.1016/j.jcjd.2014.05.006. Epub 2014 Sep 3.

Abstract

Diabetic nephropathy is the most common cause of end-stage renal disease requiring chronic dialysis or renal transplantation, resulting in high morbidity, mortality and societal costs to Canadians. Unfortunately, glycemic targets are often not achieved, and existing medications that block the renin-angiotensin-aldosterone system only offer partial protection against the development of renal and cardiovascular complications. As a consequence, in type 1 diabetes mellitus, 20% of patients treated with angiotensin-converting enzyme inhibition still have progressive nephropathy over 10 years. More recent work has suggested that blockade of renal sodium-glucose cotransport-2 (SGLT2) improves glycemic control and also reduces blood pressure, suggesting a potential for protective effects. Furthermore, in patients with type 1 diabetes, we have shown that SGLT2 inhibition reduces hyperfiltration, which is a risk factor for diabetic kidney disease and vascular dysfunction. Because primary prevention with renin-angiotensin-aldosterone system blockers have been ineffective in type 1 diabetes, early intervention studies that target alternative pathogenic mechanisms are of the utmost importance. SGLT2 inhibition may represent a safe, novel therapy that simultaneously reduces hyperglycemia, hyperfiltration and blood pressure, leading to renal and cardiovascular protection.

Keywords: SGLT2 inhibition; blood pressure; diabète de type 1; fonctionnement hémodynamique; hemodynamic function; hyperfiltration; hyperglycemia; hyperglycémie; inhibition du SGLT2; pression artérielle; renin-angiotensin-aldosterone system; rétroaction tubuloglomérulaire; système rénine-angiotensine-aldostérone; tubuloglomerular feedback; type 1 diabetes.

Publication types

  • Review

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Canada / epidemiology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / prevention & control
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Disease Progression
  • Glomerular Filtration Rate
  • Humans
  • Hyperglycemia / prevention & control
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / prevention & control
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors