CONGRESS ABSTRACT

Semaglutide is currently an approved drug to treat diabetes II and obesity. It can increase release of insulin and inhibit release of glucagon in the pancreas. It is unknown whether it exerts positive inotropic effects in the human heart. Therefore, we studied in isolated electrically stimulated 1 Hz right atrial preparations from patients that underwent open heart surgery, force of contraction under isometric conditions in buffer solution. We noted the semaglutide and liraglutide increased force of contraction starting at 10 nM and maximally at 100 nM by about 85 % (the highest concentration studied, n=8, 0.05). These effects semaglutide were accompanied by a reduction in the time of relaxation. The positive inotropic effects of semaglutide were antagonized by 1 µM exenadin, an antagonist at glucagon-like peptide-1 receptors (GLP-1R) and were less than induced by 10 µM isoprenaline which maximally stimulated β-adrenoceptors. The positive inotropic effect were potentiated (starting at 3 nM) by pre-incubation with 1 µM cilostamide, a phosphodiesterase IV inhibitor. Under the same experimental conditions glucagon increased force of contraction but via glucagon receptors. Our data suggest that at therapeutic concentrations semaglutide can stimulate force of contraction via a cAMP dependent pathway starting with the GLP-1R. Clinically, our results suggest that semaglutide via increases in cAMP content in the atrium might induce atrial fibrillation.