Insulin resistance is a risk factor for cardiovascular disease. Therapies to lower blood pressure should not decrease insulin sensitivity. Some b-adrenergic blocking agents can have an adverse effect on insulin sensitivity. This study examined the effect of extended-release metoprolol succinate on insulin sensitivity. Nondiabetics with hypertension (N=30) were started on (or changed to) hydrochlorothiazide (HCTZ) 12.5 mg daily for 14 days. Patients with blood pressure>140/90 mm Hg while taking HCTZ alone underwent an insulin clamp procedure to quantify insulin sensitivity. Metoprolol succinate treatment was begun at 50 mg daily and titrated to a dose that lowered blood pressure to <140/90 mm Hg. Following 12 weeks of metoprolol succinate plus HCTZ therapy, the insulin clamp procedure was repeated. On metoprolol succinate plus HCTZ treatment, there were no significant changes in insulin clamp measures of insulin sensitivity. Plasma cholesterol and low-density lipoprotein cholesterol decreased significantly on metoprolol succinate plus HCTZ. When b-blocker therapy is considered, metoprolol succinate can be used to treat hypertension without adverse metabolic effects.