Whether sodium-glucose cotransporter-2 inhibitors improve exercise capacity in individuals at risk of heart failure remains uncertain. A randomized clinical trial published in the American Heart Journal evaluated the effects of empagliflozin on maximal oxygen consumption (VO₂ max), daily physical activity, and quality of life in older adults with overweight or obesity and risk factors for heart failure.

This investigator-initiated, double-blind, placebo-controlled multicenter trial enrolled adults with body mass index (BMI) >28 kg/m² and at least one additional heart failure risk factor, including hypertension, ischemic heart disease, stroke, or chronic kidney disease. Participants with heart failure or type 2 diabetes mellitus were excluded. A total of 191 individuals were randomized to empagliflozin (n = 94) or placebo (n = 97) for 180 days. The primary endpoint was the mean change in VO₂ max. Secondary outcomes included objectively measured physical activity, while quality of life (QoL) was assessed as an exploratory outcome.

Among participants, 69% were men, the median age was 68 years, and the median BMI was 31.9 kg/m². Hypertension was present in 89% and ischemic heart disease in 66%. Mean left ventricular ejection fraction was 65 ± 9%, and mean VO₂ max was 18.1 ± 4.3 mL/min/kg. After 180 days, empagliflozin did not significantly change VO₂ max compared with placebo (estimated treatment difference −0.2 mL/min/kg; 97.5% CI −1.2 to 0.8; adjusted P = 1.00). No significant differences were observed in daily physical activity or QoL.

Empagliflozin treatment did not improve VO₂ max, daily physical activity, or quality of life over 180 days in older adults with overweight or obesity and risk factors for heart failure.