Dapagliflozin does not impair microvascular hemorheology in type 2 diabetes mellitus: A multicenter randomized controlled trial (D‐ PATH study)

AIMS: Sodium-glucose cotransporter 2 inhibitors reduce cardiovascular and renal events beyond glucose lowering, but their hematocrit-raising effects raise concerns about increased blood viscosity and microvascular impairment. We investigated whether dapagliflozin adversely affects microvascular hemorheology in patients with type 2 diabetes. MATERIALS AND METHODS: In this multicenter, open-label, randomized controlled trial, 82 adults with type 2 diabetes received dapagliflozin (5 mg/day) or conventional therapy for 16 weeks. The primary endpoint was the change in whole blood passage time (WBPT), measured using a microchannel flow analyzer that simulates precapillary arterioles (7 × 7 μm), with a prespecified noninferiority margin of 6.0 s (15%). Secondary outcomes included apparent microvascular viscosity, adhesive leukocyte count, and oxidative stress markers. Serum erythropoietin (EPO) was evaluated in an ancillary analysis. RESULTS: WBPT changed minimally in the dapagliflozin group (+1.4 s; 95% CI, 0.0-2.9) and slightly decreased in the control group (-0.6 s; 95% CI, -1.9 to 0.6), yielding a between-group difference of 2.0 s (95% CI, -0.2 to 3.9), with the upper bound below the prespecified noninferiority margin. Microvascular viscosity, hematocrit-standardized viscosity, leukocyte adhesion, and oxidative stress markers remained stable in both groups. Dapagliflozin increased hematocrit and EPO, particularly in participants with lower baseline hematocrit, whereas those with hematocrit >45% showed minimal change. CONCLUSIONS: Dapagliflozin did not impair microvascular hemorheology despite modest increases in hematocrit and EPO. These findings support the microvascular safety of dapagliflozin and reinforce its role in cardio-renal risk management in type 2 diabetes.