Background: In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggests that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters.

Aim: This study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index (SVRI), cardiac index (CI), stroke volume index (SVI), and heart rate (HR).

Methods: In this prospective, placebo-controlled, double blind, randomized, 2-arm parallel, interventional and exploratory study 44 patients with T2D were randomized into 2 groups and received empagliflozin 10 mg or placebo for a period of 3 months in addition to their concomitant medication. We used ClearSight System® (Edwards Lifesciences, Irvine, USA) as a validated non-invasive tool based on pulse contour analysis to examine the effects of empagliflozin on hemodynamic parameters including SVRI, CI, SVI, and HR after 1 day, 3 days and 3 months of treatment. 

Results: Baseline characteristics were comparable in the empagliflozin (n=20) and placebo (n=22) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 hrs; day 1: 48.4 ± 34.7 g/24 hrs, p<0.001) as well as urinary volume (1740 ± 601 mL/24 hrs to 2112 ± 837 mL/24 hrs, p=0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of SVRI (baseline: 1841 ± 379 dyne*sec*cm^-5*m^-2; day 1: 1864 ± 373 dyne*sec*cm^-5*m^-2, p=0.411; day 3: 1837 ± 376 dyne*sec*cm^-5*m^-2, p=0.991; month 3: 1908 ± 451 dyne*sec*cm^-5*m^-2, p=0.795), nor on CI, SVI or HR at any time point. Over time, blood pressure was reduced in empagliflozin-treated participants but the effect did not reach statistical significance.

Conclusion: Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months.