124-OR: Effects of Dapagliflozin Therapy on Renal Hemodynamics in Type 2 Diabetes Patients

Aim: To investigate the renal hemodynamic effects of SGLT-2i therapy in patients with type 2 diabetes [T2D].

Design & Methods: We recruited 24 drug naïve T2D, not receiving ACEi/ARBs. GFR [>100ml/min/1.73m²] was measured with Iohexol clearance and renal plasma (blood) flow [RP(B)F] with PAH clearance divided by (1-Hct). Mean arterial pressure [MAP] and renal vascular resistance [RVR] were determined before and 4 months after dapagliflozin 10mg/day (DAPA, n=12); results were compared to T2D receiving metformin±glipizide to achieve similar glycemic reduction (CONTROL, n=12).

Results: HbA1c decreased equally in DAPA (8.2±0.2 to 7.1±0.2%) and CONTROL (8.4±0.3 to 7.2±0.1%); body weight decreased in DAPA (89.9±4.0 to 86.2±4.2 kg) and rose in CONTROL (86.5±6.2 to 88.9±5.5 kg). GFR [ml/min/1.73m²] declined in DAPA (118±5 to 103±5) but not in CONTROL (113±6 vs. 114±7) (p<0.01). RPF [ml/min] did not change in DAPA (668±65 vs. 676±70) and CONTROL (630±40 vs. 629±39), while filtration fraction [FF] decreased in DAPA (18±1 vs. 15±1%) but not in CONTROL (18±2 vs. 18±2%) (p<0.05). MAP [mmHg] declined in DAPA (95.4±2.6 vs. 89.9±2.5) but not in CONTROL (90.3±4.1 vs. 90.7±2.1) (p<0.05). Thus, calculated RVR [mmHg/L/min] in DAPA decreased (87.0±4.2 to 77.6±2.9), whereas it did not change (86.2±3.8 to 86.4±4.2) in CONTROL after 4 months of therapy (p<0.05).

Conclusion: Despite equal glycemic control, treatment with dapagliflozin, but not with metformin+glipizide, reduced glomerular filtration fraction and renal vascular resistance. Thus, unlike studies in T1D, our data suggest that in T2D post-glomerular vasodilatation is the predominant reno-protective mechanism of SGLT-2 inhibitors. Concomitant pre-glomerular vasoconstriction, however, cannot be excluded.