title: Nateglinide improves early insulin secretion and controls postprandial glucose excursions in a prediabetic population.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the metabolic effectiveness, safety, and tolerability of nateglinide in subjects with impaired glucose tolerance (IGT) and to identify a dose appropriate for use in a diabetes prevention study.
  
  
  METHODS
  This multicenter, double-blind, randomized, parallel-group, fixed-dose study of 8 weeks' duration was performed in a total of 288 subjects with IGT using a 2:2:2:1 randomization. Subjects received nateglinide (30, 60, and 120 mg) or placebo before each main meal. Metabolic effectiveness was assessed during a standardized meal challenge performed before and after the 8-week treatment. All adverse events (AEs) were recorded, and confirmed hypoglycemia was defined as symptoms accompanied by a self-monitoring of blood glucose measurement < or =3.3 mmol/l (plasma glucose < or =3.7 mmol/l).
  
  
  RESULTS
  Nateglinide elicited a dose-related increase of insulin and a decrease of glucose during standardized meal challenges, with the predominant effect on early insulin release, leading to a substantial reduction in peak plasma glucose levels. Nateglinide was well tolerated, and symptoms of hypoglycemia were the only treatment-emergent AEs. Confirmed hypoglycemia occurred in 28 subjects receiving nateglinide (30 mg, 0 [0%]; 60 mg, 5 [6.6%]; 120 mg, 23 [26.7%]) and in 1 (2.3%) subject receiving placebo.
  
  
  CONCLUSIONS
  Nateglinide was safe and effective in reducing postprandial hyperglycemia in subjects with IGT. Preprandial doses of 30 or 60 mg nateglinide would be appropriate to use for longer-term studies to determine whether a rapid-onset, rapidly reversible, insulinotropic agent can delay or prevent the development of type 2 diabetes.
authors.affiliation: Helsinki University Hospital, Department of Medicine, Finland.
authors.forename: Carola
authors.initials: C
authors.lastname: Saloranta
authors.forename: Christiane
authors.initials: C
authors.lastname: Guitard
authors.forename: Eckhard
authors.initials: E
authors.lastname: Pecher
authors.forename: Pedro
authors.initials: P
authors.lastname: De Pablos-Velasco
authors.forename: Kaj
authors.initials: K
authors.lastname: Lahti
authors.forename: Patrick
authors.initials: P
authors.lastname: Brunel
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D003510:Cyclohexanes / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D019518:Postprandial Period; D011236:Prediabetic State / Q000097:blood* / Q000188:drug therapy*
chemical_list: D001786:Blood Glucose; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine