title: Synergistic effect of doxazosin and acarbose in improving metabolic control in patients with impaired glucose tolerance.
abstract: OBJECTIVE
  The aim of this study was to evaluate if the expected improvement in glucose and lipid metabolism obtainable with doxazosin is or is not synergistic with standard antihyperglycaemic treatment using the alpha-glucosidase inhibitor acarbose.
  
  
  METHODS
  Patients in this randomised, controlled, double-blind clinical trial were enrolled, evaluated and followed up at three Italian centres. We evaluated 107 patients (53 males and 54 females) with impaired glucose tolerance (IGT) as determined by oral glucose tolerance tests (OGTTs). All patients took a fixed dose of acarbose 150 mg/day for 3 months, after which they were titrated up to 300 mg/day for the next 3 months. In addition, patients were randomised to either placebo (53 patients: 27 males and 26 females, aged 50 +/- 4 [mean +/- SD] years) or doxazosin 4 mg/day (54 patients: 26 males and 28 females, aged 51 +/- 5 years) for the entire 6-month treatment period. Parameters evaluated during the 6-month treatment period included body mass index (BMI), glycaemic control (glycosylated haemoglobin [HbA(1c)], fasting plasma [FPG] and post-prandial plasma [PPG] glucose, fasting plasma [FPI] and post-prandial plasma [PPI] insulin levels, homeostasis model assessment [HOMA]-index [insulin resistance]), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and systolic (SBP) and diastolic (DBP) blood pressure.
  
  
  RESULTS
  Significant reductions in BMI, HbA(1c), FPG and PPG compared with baseline were observed after 6 months in both groups (p < 0.05). A significant decrease in FPI was obtained after 6 months (p < 0.05) in the doxazosin group compared with baseline, and this difference was also significant (p < 0.05) compared with the placebo group. Similarly, a significant decrease in HOMA-index was observed at 6 months (p < 0.05) compared with baseline in the doxazosin group, and this difference was also significant (p < 0.05) compared with the placebo group. Significant decreases in TC, LDL-C, HDL-C and TG (p < 0.05) were observed in the doxazosin group after 6 months compared with baseline values. Significant decreases in SBP and DBP were also observed at 3 months in the doxazosin group compared with baseline (p < 0.05), and these differences were significant (p < 0.05) compared with placebo. Furthermore, significant decreases in SBP and DBP were observed at 6 months (p < 0.01) in the doxazosin group compared with baseline, and these differences were also significant (p < 0.01) compared with placebo. All patients who completed an OGTT at 6 months (96 patients) were restored to normal glucose tolerance status.
  
  
  CONCLUSIONS
  In patients with IGT, doxazosin given in combination with acarbose seemed to improve glycaemic and lipid control compared with placebo, with the benefits observed appearing to extend beyond those expected from improvements in blood pressure. Patients in this study also benefited from acarbose therapy, which restored all patients from IGT to normal glucose tolerance status.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. giuseppe.derosa@unipv.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
authors.forename: Arrigo F G
authors.initials: AF
authors.lastname: Cicero
authors.forename: Angela
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Pietro D
authors.initials: PD
authors.lastname: Ragonesi
authors.forename: Leonardina
authors.initials: L
authors.lastname: Ciccarelli
authors.forename: Elena
authors.initials: E
authors.lastname: Fogari
authors.forename: Sibilla A T
authors.initials: SA
authors.lastname: Salvadeo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrari
authors.forename: Alessia
authors.initials: A
authors.lastname: Gravina
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fassi
authors.forename: Roberto
authors.initials: R
authors.lastname: Fogari
mesh_terms: D020909:Acarbose / Q000008:administration & dosage*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D004311:Double-Blind Method; D017292:Doxazosin / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008055:Lipids; D017292:Doxazosin; D020909:Acarbose