Effect of delapril/manidipine vs olmesartan/ hydrochlorothiazide combination on insulin sensitivity and fibrinogen in obese hypertensive patients.
OBJECTIVE
To compare the effect of delapril/manidipine vs olmesartan/hydrochlorothiazide (HCTZ) combination on insulin sensitivity and plasma fibrinogen in obese hypertensive patients.


METHODS
After a 4-week placebo period, 88 obese, hypertensive (DBP >95 and <110 mmHg) outpatients were randomized to delapril 30 mg/manidipine 10 mg combination or to olmesartan 20 mg/HCTZ 12.5 mg combination for 24 weeks according to a prospective, randomized, open-label, blinded endpoint, parallel group design. At the end of the placebo period and treatment period, clinical BP, fasting plasma glucose (FPG), plasma insulin, insulin sensitivity (by euglycemic hyperinsulinemic clamp) and plasma fibrinogen were evaluated. Insulin sensitivity was expressed as the amount of glucose infused during the last 30 minutes (glucose infusion rate, GIR) in mg/Kg/min. The total glucose requirement (TGR) to maintain a steady-state blood glucose level in response to a defined increase in plasma insulin concentration was also evaluated.


RESULTS
Both combinations significantly reduced SBP/DBP values (-22.3/16.4 mmHg and -22.6/17.2 mmHg, respectively, all p <0.001 vs placebo). GIR was significantly increased only by delapril/manidipine (+3.01 mg/min/Kg, p=0.038 vs placebo), the difference between treatments being significant (p <0.05). TGR was significantly increased by delapril/manidipine (+9.7 g, p=0.034), while it was unaffected by olmesartan/HCTZ. Plasma insulin as well as fibrinogen were significantly reduced by delapril/manidipine (-17.8 pmol/l, p=0.047 and -67.5 mg/dl, p=0.021, respectively), but not by olmesartan/HCTZ, the difference between the two treatments being statistically significant (p <0.05).


CONCLUSIONS
In obese hypertensive patients the delapril/manidipine combination but not the olmesartan/HCTZ combination significantly decreased insulin resistance and plasma fibrinogen levels, despite the similar BP lowering efficacy.
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
Derosa
Giuseppe
G
Zoppi
Annalisa
A
Lazzari
Pierangelo
P
Corradi
Luca
L
Preti
Paola
P
Mugellini
Amedeo
A
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D005340:Fibrinogen / Q000187:drug effects*; D015309:Glucose Clamp Technique; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009578:Nitrobenzenes; D009765:Obesity / Q000150:complications*; D010879:Piperazines; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004338:Drug Combinations; D007093:Imidazoles; D007189:Indans; D009578:Nitrobenzenes; D010879:Piperazines; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C054218:manidipine; C437965:olmesartan; D005340:Fibrinogen; C047759:delapril