Empagliflozin (EMPA) Enhances Vascular Insulin Sensitivity and Lowers Plasma ICAM in Subjects with Type 2 Diabetes (T2D)

Background: The mechanism(s) by which sodium-glucose cotransporter 2 inhibitor (SGLT2i) use improves cardiovascular and renal outcomes in T2D are not well-defined. We hypothesized that EMPA would increase vascular insulin sensitivity and decrease endothelial cell (EC) stress markers in T2D. Study Design: Ten 18-60 years-old persons with T2D, 6.5 < a1c 3 months, were studied. we measured vascular stiffness (pulse wave separation analysis), ec function (flow-mediated dilation (fmd)), and stress biomarkers (elisa) before after a 2-hour, 1 mu min kg euglycemic clamp at 0 12 weeks treatment with 10 mg empa daily. results: not wk 0, but wks, insulin decreased forward backward arterial pressures from 28±3 to 20±2 24±3 13±1 mmhg, respectively, (p<0.02, each) improved the fmd response (p="0.02)," indicating function. peripheral systolic diastolic unchanged by week declined (p<0.03, treatment. lowered baseline post-insulin plasma icam-1 (p<0.002, increased vcam-1 (p<0.0005). infusion pecam-1 (p<0.03) vasoconstrictor endothelin-1 (p<0.01) comparably or without e-selectin s100a8 9 did change significantly either empa. decrease suggests that inflammation. insulin’s action lower appeared independent of empa, may contribute empa’s beneficial actions. Interpretation: EMPA for 12 weeks enhanced insulin’s action to: 1) diminish arterial stiffness, 2) enhance EC function including biomarker release, and 3) lower blood pressure. Improved vascular insulin sensitivity may contribute to the improved CVD outcomes seen with SGLTi treatment. Disclosure T.Nguyen: None. L.Jahn: None. L.Hartline: None. K.W.Aylor: None. E.Barrett: None. Funding National Institutes of Health (R01HL142250)