To evaluate the interactions between the weight loss drug, sibutramine, and different antihypertensive treatments, we randomly assigned 171 subjects taking 3 antihypertensive treatment regimens to receive sibutramine or placebo. Our study showed for the first time that combination therapy with an angiotensin-converting enzyme inhibitor and a calcium channel blocker is more advantageous than a ß blocker/diuretic-based-regimen with regard to supporting the weight-reducing actions and metabolic changes induced by sibutramine.