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.


CONCLUSIONS
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.
Fogari
Roberto
R
Department of Internal Medicine and Therapeutics, Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Italy. r.fogari@unipv.it
Preti
Paola
P
Zoppi
Annalisa
A
Mugellini
Amedeo
A
Corradi
Luca
L
Lazzari
Pierangelo
P
Santoro
Tara
T
Derosa
Giuseppe
G
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D050177:Overweight / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
D007328:Insulin; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine