LY377604 + sibutramine

**LY377604 + sibutramine** is an experimental oral combination drug developed for the treatment of obesity. LY377604 is a selective beta adrenoceptor modulator that functions as a potent β3-adrenergic receptor agonist and as an antagonist at β1- and β2-adrenergic receptors, without sympathomimetic activity at β1 or β2. Sibutramine is a norepinephrine and serotonin reuptake inhibitor which, on its own, can increase blood pressure and heart rate as a side effect. LY377604 was combined with sibutramine to enhance weight loss and to counteract sibutramine’s cardiovascular side effects by blocking β1- and β2-adrenergic receptors. The combination demonstrated potential benefit by reducing increases in heart rate and blood pressure in human trials, and was studied in phase II clinical trials for obesity, but was never marketed[1][2][3][4][5].