857-P: Mechanisms of Dapagliflozin to Reduce Intraglomerular Pressure in Patients with Type 2 Diabetes

Abstract

Aim: To examine the renal hemodynamic effects of SGLT-2i therapy in type 2 diabetes patients [T2D]. Design & Methods: T2D (n=20) with normal GFR measured with 24-hour creatinine clearance [CrCl>100ml/min/1.73m2], who were not receiving ACEi or ARB, had renal blood flow (RBF) measured using PAH clearance divided by (1-Hct) and mean arterial pressure [MAP] to calculate renal vascular resistance [RVR] prior to and 4 months after Dapagliflozin 10mg/day (DAPA, n=10) . Results were compared to T2D treated with metformin ± glipizide to achieve similar glycemic control (Control, n=10) . Results: HbA1c decreased equally in DAPA (8.6±0.5% to 7.4±0.3%) and CONTROL (8.7±0.3 to 7.5±0.2%) . There was a non-significant increase in RBF (ml/min) in DAPA compared to Control. MAP (mmHg) decreased by 8.5% from 98.4±2.9 mmHg to 90.0±2.0 mmHg and RVR by 21.4% from 87.9±5.1 mmHg/l/min to 69.1±5.2 mmHg/l/min in the DAPA group, while MAP & RVR remained unchanged in CONTROL group. Data at baseline [Pre-Rx] and after 4 months of therapy [Post-Rx] are shown in the table. Conclusion: These findings show that, with equivalent glycemic control, dapagliflozin, but not metformin/glipizide, is accompanied by a decrease in renal vascular resistance, without significant change in RBF. Unlike studies in T1D, our results suggest that in T2D patients post-glomerular vasodilatation is the primary reno-protective mechanism of SGLT-2i therapy. Disclosure M.Barkhordarian: None. C.L.Triplitt: Consultant; Bayer AG, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. C.Solis-herrera: Speaker's Bureau; Novo Nordisk. J.M.Adams: None. R.A.Defronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Speaker's Bureau; AstraZeneca. E.Cersosimo: Research Support; AstraZeneca. Funding AstraZeneca