Subjects with type 2 diabetes experience an increased cardiovascular morbidity and mortality, related to a high prevalence of hypertension, dyslipidemia, and obesity. Antihypertensive treatment with beta-adrenergic receptor blockers may have deleterious metabolic consequences, including worsening of lipid profiles and insulin sensitivity. The centrally-acting sympatholytic agent moxonidine may improve these variables. In this randomised, double-blind multicenter study, the effects of two widely used antihypertensive agents--moxonidine (MOX) and the beta (1)-selective adrenergic receptor blocker metoprolol (MET)--on blood pressure and metabolic control were directly compared in hypertensive subjects with type 2 diabetes. Patients received either MOX (0.2 - 0.6 mg/d) or MET (50 - 150 mg/d) for 12 weeks, intending comparable blood pressure control. In total 200 patients were randomized. Here we report results from the per protocol population consisting of 127 patients (MOX 66, MET 61) but similar results were found in the ITT population. Reductions in systolic (SBP) and diastolic (DBP) blood pressures after 12 weeks were similar in both groups: In the MOX group, mean SBP (+/- SD) decreased from 154 +/- 12 to 142 +/- 17 mmHg and mean DBP from 91 +/- 9 to 83 +/- 9 mmHg. In the MET group, mean SBP decreased from 152 +/- 13 to 140 +/- 15 mmHg, and mean DBP from 90 +/- 8 to 84 +/- 10 mmHg. Mean HbA (1C) values did not differ between groups after 12 weeks (MOX 8.1 +/- 1.4 Hb%, MET 8.1 +/- 1.5 Hb%, intention-to-treat population). However, fasting plasma glucose decreased in the MOX group (median change - 5 mg/dl), but increased in the MET group (+ 16 mg/dl; p < 0.05). Median changes in the insulin resistance index (HOMA (IR)) were + 0.56 micro IU x mol/L (2) in the MET group, and - 0.27 micro IU x mol/L (2) in the MOX group. Correspondingly, fasting triglycerides increased with a median change of + 29.5 mg/dL in the MET group, but decreased in the MOX group (- 27.5 mg/dl; p < 0.05). These results indicate that MOX, unlike MET, may elicit beneficial adaptations in glucose and lipid metabolism in hypertensive subjects with type 2 diabetes, although mean HbA (1c) values did not differ. In long-term treatment in this high-risk population, MOX thus may decrease global vascular disease risk to a greater extent than MET.