Renal Hemodynamic Effect of Sodium Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus
Background The primary objective of this mechanistic open label, stratified clinical trial was to determine the effect of 8 weeks' sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus (T1D) Methods and Results Inulin (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma flow) clearances were measured in individuals stratified based on having hyperfiltration (T1D H, GFR 135 mL/min/1.73m2, n=27) or normal GFR (T1D N, GFR 90 134 mL/min/1.73m2, n=13) at baseline. Renal function and circulating levels of renin angiotensin aldosterone system mediators and NO were measured under clamped euglycemic (4 6 mmol/L) and hyperglycemic (9 11 mmol/L) conditions at baseline and end of treatment. During clamped euglycemia, hyperfiltration was attenuated by 33 mL/min/1.73m2 with empagliflozin in T1D H, (GFR 172+ 23 139+ 25 mL/min/1.73 m2, P<0.01) This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance (all P<0.01) Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia. In T1D N, GFR, other renal function parameters, and plasma NO were not altered by empagliflozin. Empagliflozin reduced hemoglobin A1c significantly in both groups, despite lower insulin doses in each group (P0.04) Conclusions In conclusion, short term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin attenuated renal hyperfiltration in subjects with T1D, likely by affecting tubular glomerular feedback mechanisms. Clinical Trial Registration URL: http:/www.clinicaltrials.gov. Unique identifier: NCT01392560.
Circulation