Effects of empagliflozin on cardiac function and cardiorespiratory fitness in people with type 2 diabetes: a randomised controlled trial

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in adults with type 2 diabetes mellitus (T2DM). Cardiac dysfunction and decreased exercise capacity are common in people with T2DM, even in those without overt heart failure. Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, reduces major cardiovascular events and mortality in people with T2DM and established CVD, though the underlying mechanisms are not fully elucidated. This study aimed to assess changes in cardiac function and cardiorespiratory fitness (CRF) at rest and during exercise with empagliflozin treatment in people with T2DM. This double-masked, single-centre, randomised, placebo-controlled analysis combined two studies involving adults (≥ 18 years) with T2DM comparing empagliflozin 25 mg daily vs. placebo, each over three months. VO₂ peak was measured using a ramp protocol peak exercise test on a bicycle ergometer, and echocardiography assessed changes in cardiac structure and function. Of 65 recruited participants, 57 completed the study (70.2% male, age 64.9 ± 7.8 year, baseline HbA1c 7.8% (7.5–8.4). Thirty-one participants (67.7% male, age 65.6 ± 6.6 year) were randomised to the placebo group, and 26 participants (73.1% male, age 64.2 ± 9.0 year) were randomised to empagliflozin. No significant between-group difference in the primary outcome of change in VO2 peak was observed. Empagliflozin reduced left ventricular end-diastolic volume (LVEDV) at rest by 9.508 ± 14.54 mL compared with placebo, which increased by 2.13 ± 20.73 mL (p = 0.0232). In adults with T2D, 12 weeks of empagliflozin significantly reduced LVEDV without changing VO2 peak. Empagliflozin may enhance cardiovascular efficiency without directly improving functional capacity. ACTRN12617000490370p & ACTRN12619000887178.