Aim: To investigate the benefits of dapagliflozin [DAPA] on renal hemodynamics in type 2 diabetes patients [T2D] with glomerular hyperfiltration.

Design and Methods: 24 T2D with elevated [HYPER] and normal [NORMO] GFR, measured by Iohexol, randomized to either DAPA, 10mg/day [DAPA/HYPER, n=6; DAPA/NORMO, n=6] or metformin+glipizide [CON/HYPER, n=6; CON/NORMO, n=6] for 4 months. Hyperfiltration was defined as GFR>125ml/min/1.73m2. Renal plasma (blood) flow [RP(B)F] measured with PAH divided by (1-Hct), mean arterial pressure [MAP], filtration fraction [FF] and renal vascular resistance [RVR] were determined before and after treatment.

Results: A1c[%] decreased similarly in DAPA/HYPER (8.3±0.2 vs. 6.8±0.2), CON/HYPER (8.7±0.3 vs. 7.2±0.1), DAPA/NORMO (8.6±0.3 vs. 7.3±0.2) and CON/NORMO (8.2±0.3 vs. 7.4±0.2). Body weight[Kg] was reduced in DAPA/HYPER (89±4 vs. 84±4) and DAPA/NORMO (90±3 vs. 87±2) but not in CON/HYPER (86±4 vs. 87±3) and CON/NORMO (87±4 vs. 91±3) (p<0.05). GFR declined by 17% in DAPA/HYPER and by 8% in DAPA/NORMO (both, p<0.05) but did not change in CON. FF and RVR fell in DAPA but not in CON. Renal hemodynamics at baseline [PRE-Tx] and after 4 months [POST-Tx] are shown in the table.

Conclusion These results indicate that dapagliflozin, but not metformin+glipizide therapy, normalizes glomerular hyperfiltration and reduces renal vascular resistance in hyperfiltering type 2 diabetes patients.

Disclosure

G.Baskoy: None. Y.Qin: None. E.Cersosimo: None. C.Solis-herrera: None. J.M.Adams: None. R.A.Defronzo: Advisory Panel; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Novo Nordisk, Research Support; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc., Speaker's Bureau; AstraZeneca. C.L.Triplitt: Speaker's Bureau; Novo Nordisk.

Funding

AstraZeneca; Texas Diabetes Institute

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