title: The NEPI antidiabetes study (NANSY). 1: short-term dose-effect relations of glimepiride in subjects with impaired fasting glucose.
abstract: OBJECTIVE
  NANSY is a randomised, placebo-controlled Swedish-Norwegian study which aims to include 2 x 1112 male and female subjects with impaired fasting glucose (IFG), to assess whether conversion to type 2 diabetes can be delayed by addition of sulphonylurea to dietary regulation and increased exercise. This pilot study was conducted to find the optimum dose of glimepiride in NANSY.
  
  
  METHODS
  In a double blind trial in primary care 25 IFG subjects were in random order exposed to single doses and one-week treatments with 0 (placebo), 0.5, 1.0 and 2.0 mg glimepiride once daily. The optimum dose was assessed by measuring blood glucose during oral 75 g glucose tolerance test (OGTT), comparing fasting blood glucose, and the area under the blood glucose curve (AUC), and by monitoring hypoglycaemic events.
  
  
  RESULTS
  With single doses, there was a clear dose-response relationship for the reduction in AUC, with a statistically significant difference only between placebo (mean 1981, 95% confidence intervals (CI) 1883-2078) and 2 mg glimepiride (mean 1763, 95% CI 1665-1861). However, following 1-week treatments, the only significant difference was between placebo (mean 1934, 95% CI 1856-2012) and 1 mg glimepiride (mean 1714, 95% CI 1637-1792). Correspondingly, the only statistically significant difference in fasting blood glucose day 7 was between placebo (5.87 mmol/l, 95% CI 5.68-6.05 mmol/l) and 1 mg glimepiride (5.42 mmol/l, 95% CI 5.21-5.62 mmol/l). Chemical hypoglycaemia was common but hypoglycaemic symptoms were rare and similar between the active doses, and easily countered by the subjects.
  
  
  CONCLUSIONS
  The sulphonylurea dose-effect curve may be bell-shaped, perhaps due to down regulation of sulphonylurea receptors during chronic exposure. Alternatively, the finding could be a rebound phenomenon, secondary to preceding hypoglycaemia. The optimum dose for NANSY was found to be 1 mg glimepiride.
authors.affiliation: Skaraborg Institute, Skövde, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Lindblad
authors.forename: K
authors.initials: K
authors.lastname: Lindwall
authors.forename: A
authors.initials: A
authors.lastname: Sjöstrand
authors.forename: J
authors.initials: J
authors.lastname: Ranstam
authors.forename: A
authors.initials: A
authors.lastname: Melander
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001824:Body Constitution; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D018149:Glucose Intolerance / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009664:Norway; D010919:Placebos; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D013548:Sweden; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D010919:Placebos; D013453:Sulfonylurea Compounds; D014280:Triglycerides; C057619:glimepiride; D002784:Cholesterol