Background: Cardioprotective benefits of SGLT2 inhibitors (SGLT2i) are well established. However, their effects on cardiopulmonary function measured by CPET in patients with T2D and HFrEF continue to be largely unknown.

Objective: Examine the effects of SGLT2i on cardiopulmonary function measured by cardiopulmonary exercise test (CPET) & 6MWT in patients with T2D & HFrEF.

Methods: Six subjects with T2D with HFrEF (<40%) (Age=59±2.6, BMI=33.3±1.1, A1c=7.1±0.3, EF 28±4%) were randomized to empagliflozin 25mg (SGLT2i) vs. placebo in a 2:1 fashion for 12 weeks. Cardiac MRI, 6MWT, and CPET were performed pre- and post-intervention.

Results: SGLT2i group showed an increase in EF. All subjects reached submaximal cardiovascular effort (RER≤1.10). The Ventilatory Anaerobic Threshold (VT, submaximal index of exercise capacity) showed a significant increase in VT time with SGLT2i (p=0.05). The rest of the parameters trended toward improvement including Ve/VCO2 slope and 6MWT.

Conclusion: Subjects with T2D and HFrEF, treated with an SGLT2i had improved EF, a decrease in the worsening of the Ve/VCO2 slope (a predictor of mortality in HF patients), an increase in 6MWT, and significantly improved VT time (aerobic metabolism) compared to placebo. These findings may represent a novel mechanism of CV protection and warrants further investigation.

Disclosure

Y. Qin: None. C. L. Triplitt: Speaker's Bureau; Novo Nordisk. G. D. Clarke: None. E. Cersosimo: None. S. E. Espinoza: 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. Solis-herrera: None. F. M. Acosta: None. S. Neppala: None. T. M. Cortes: None. A. Stepanenko: None. A. Moody: None. N. D. Sanchez: None. M. Brown: None. L. A. Cruz moreno: None.

Funding

Doris Duke Charitable Foundation; Voelcker Foundation; National Institutes of Health

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