How does dapagliflozin affect cardiac function, hormonal responses to exercise?

Growth hormone (GH), compared with catecholamines, appears to be a better facilitator for the change from glucose to fatty acid metabolism following SGLT2 inhibitor use during exercise, reveals a study.

A double-blind, placebo-controlled study with a 4-week washout period was conducted to examine the effect of the SGLT2 inhibitor dapagliflozin (DAPA) on cardiac function and the metabolic and hormonal response to moderate exercise in people with type 2 diabetes.

The authors randomized nine participants to receive either 4 weeks of DAPA or placebo. Participants underwent an exercise protocol after each treatment, with two consecutive 10-minute stages at a constant load corresponding to 40 percent and 70 percent maximal oxygen consumption (VO_2max), coupled with hormonal and metabolic analysis.

Three years later, the authors performed a blinded transthoracic echocardiogram.

Glucose (p<0.0001) and lactate (p<0.05) were lower during the exercise protocol, while β-hydroxybutyrate (p<0.0005) and growth hormone (p=0.01) were higher following DAPA treatment relative to placebo. A trend for lower insulin was also seen with DAPA, but no difference in adrenalin, noradrenalin, and glucagon was observed.

Participants showed a higher mean peak diastolic mitral annular velocity (e’) following DAPA when compared to placebo (p=0.03). In addition, the indexed left atrial volume and right ventricular e’ decreased after DAPA (p=0.045) compared with placebo (p=0.042).

No difference in arterial stiffness was observed between treatment groups (9.35 m/s with DAPA vs 9.07 m/s with placebo).

“The 4-week crossover design showed changes in cardiac function were rapid in onset and reversible,” the authors said.