Sodium-glucose Cotransporter 2 Inhibition in Type 1 Diabetes: Simultaneous Glucose Lowering and Renal Protection?

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.