ObjectiveTo clarify the role of insulin resistance and hyperinsulinaemia in the pathogenesis of obesity-related hypertension.DesignAn open study comparing the effects of weight reduction by low-energy diet and treatment with troglitazone, an insulin-sensitizing agent.SettingA tertiary teaching hospital.PatientsThirty overweight hypertensive patients (15 men and 15 women, mean age 61 years, mean body mass index 29.1 kg/m2).InterventionsFifteen patients were assigned to a weight-reduction programme by low-energy diet (3360 kJ/day) for 3 weeks; the remaining 15 patients were treated with troglitazone (400 mg/day) for 8 weeks.Main outcome measuresCasual and ambulatory blood pressures, glucose and lipid metabolism, and insulin sensitivity.ResultsThe baseline values of body mass index, fasting and post-glucose plasma insulin, and casual and ambulatory blood pressures were comparable between the two groups. Weight reduction (4.1 ± 0.3 kg, mean ± SEM) was associated with significant decreases in plasma insulin, blood glucose, homeostasis model assessment (HOMA) insulin resistance index, serum triglyceride, casual blood pressure (7.7 ± 2.3/3.9 ± 1.4 mmHg) and 24 h blood pressure (8.3 6 1.9/ 4.3 ± 1.1 mmHg). Treatment with troglitazone caused comparable decreases in the metabolic parameters and HOMA index, but did not change casual or 24 h blood pressure (0.8 ± 3.4/0.8 ± 2.1 and 1.5 ± 2.4/1.0 ± 1.9 mmHg, respectively).ConclusionsInsulin resistance/hyperinsulinaemia may not have an important role in the pathogenesis of obesity-related hypertension. The antihypertensive effect of weight reduction seems to be mediated mainly by other mechanisms.