Effect of Valsartan Addition to Amlodipine on Insulin Sensitivity in Overweight-Obese Hypertensive Patients

OBJECTIVE: The aim of the study was to evaluate the effect of valsartan/amlodipine combination on insulin sensitivity in overweight-obese hypertensive patients. METHODS: After a 4-week placebo period, 58 overweight-obese (BMI >or=25 kg/m(2)) patients, with mild to moderate essential hypertension (DBP >95 and <110 mmHg, SBP >140 mmHg) were treated with amlodipine 5 mg od or valsartan 160 mg od or amlodipine 5 mg plus valsartan 160 mg od for 8 weeks according to a randomized, open-label, blinded end-point, cross-over study. At the end of the placebo period and each treatment period, blood pressure (BP) and insulin sensitivity (IS) (by euglycemic hyperinsulinemic clamp technique) were evaluated. IS was expressed as the amount of glucose infused during the last 30 min (glucose infusion rate, GIR) in mg/kg/min. RESULTS: Valsartan/amlodipine combination produced a significantly greater decrease in SBP/DBP values (-22.3/16.7 mmHg, p<0.001 vs baseline) than valsartan (-15.2/11.7 mmHg, p<0.01 vs baseline) and amlodipine monotherapy (-16.1/12.6 mmHg, p<0.01 vs baseline). Both valsartan and amlodipine provided a significant increase in GIR (+1.24 mg/kg/min, p=0.036 vs baseline and +1.02 mg/kg/min, p=0.047, respectively), but such an increase was significantly greater with their combination (+1.82 mg/kg/min, p<0.01 vs baseline). These greater changes in IS were not related to BP changes. CONCLUSION: Valsartan/amlodipine combination improved IS more than respective monotherapy beyond affording greater BP reductions. This strengthens the rationale to use valsartan/amlodipine combination in the treatment of overweight-obese hypertensives.