Project Title

Cardioprotective mechanisms after termination of incretin-based treatment 

Background

Incretin-based therapies are promising in obesity treatment and reduce the risk of adverse cardiovascular events. The cardioprotective effects could be related to direct actions on inflammation, endothelial function, and ectopic fat accumulation. Treatment discontinuation leads to rapid relapse of cardiovascular health, emphasizing the need for sustainable strategies after treatment termination. 

Aim

To elucidate the cardioprotective mechanisms of incretin-based therapy and develop a strategy to discontinue incretin-based therapy while sustaining cardioprotective effects.  

Methods

Young adults with obesity will be randomized to placebo or treatment with incretin-based therapy (semaglutide). All participants who have received semaglutide or placebo will undergo a medication discontinuation plan and be re-randomized to a control group or an exercise program consisting of a combination of vigorous-intensity aerobic exercise and muscle strengthening exercises. The effects on cardiovascular health for 1) semaglutide versus placebo and 2) exercise versus control after medication termination will be assessed by extracellular vesicle profiling and changes in markers of atherosclerosis, inflammation, endothelial function, and ectopic and liver fat. 

Preliminary results

In my previous studies, I observed that people who exercised during incretin-based pharmacotherapy had sustained benefits after treatment discontinuation, suggesting a potential for structured exercise to sustain the cardioprotective effects after termination of incretin-based treatment.