Randomized Controlled Trial of the Hemodynamic Effects of Empagliflozin in Patients With Type 2 Diabetes at High Cardiovascular Risk: The SIMPLE Trial
Diabetes 2022;71:812–20 doi.org/10.2337/db21-0721
In this analysis of data from the SIMPLE trial, empagliflozin did not reduce left heart filling pressure more than placebo at submaximal exercise in patients with T2D at high CV risk. However, it was observed that empagliflozin reduced pulmonary capillary wedge pressure (PCWP) at a magnitude of clinical significance in patients at rest. The findings suggest cardiac benefits beyond the diuretic effect of sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment and could explain a significant part of the CV benefits observed in clinical trials.
Results from CV outcomes trials have shown that SGLT2i treatment significantly reduces CV events in patients with T2D, but the mechanisms remain unknown. SGLT2 inhibition is associated with increased diuresis and sodium excretion; as such, SGLT2i treatment could be beneficial in patients with increased cardiac filling pressure. This prespecified sub-study to the SIMPLE trial investigated whether SGLT2i treatment affects central haemodynamics during rest and exercise in 34 patients with T2D at high risk of CV events. Patients were randomised to empagliflozin or placebo for 13 weeks.
Haemodynamic measurements at rest and peak exercise during baseline and follow-up showed there was a significant treatment effect on diastolic pulmonary artery pressure (DPAP). Patients receiving SGLT2i also had reduced PCWP compared to those in the placebo group. The authors suggest that – contrary to the initial hypothesis – the data suggest the treatment effect is measurable at rest and weans as exercise intensity increases. The findings could explain a significant part of the CV benefits observed in clinical trials.