title: Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycemia and improves overall glycemic control.
abstract: OBJECTIVE
  To determine the effects of nateglinide added to rosiglitazone monotherapy on glycemic control and on postprandial glucose and insulin levels in patients with type 2 diabetes.
  
  
  METHODS
  This 24-week, multicenter, double-blind, randomized study compared the efficacy of nateglinide (120 mg a.c.) and placebo added to rosiglitazone monotherapy (8 mg q.d.) in 402 patients with type 2 diabetes with HbA(1c) between 7 and 11% (inclusive). Efficacy parameters tested included HbA(1c) and plasma glucose and insulin levels in the fasting state and after a standardized meal challenge. Safety data were also collected.
  
  
  RESULTS
  In placebo-treated patients, HbA(1c) did not change (Delta = 0.0 +/- 0.1%). In patients randomized to nateglinide, HbA(1c) decreased from 8.3 to 7.5% (Delta = -0.8 +/- 0.1%, P < 0.0001 vs. placebo). Target HbA(1c) (<7.0%) was achieved by 38% of patients treated with combination therapy and by 9% of patients remaining on rosiglitazone monotherapy. In nateglinide-treated patients, fasting plasma glucose levels decreased by 0.7 mmol/l, 2-h postprandial glucose levels decreased by 2.7 mmol/l, and 30-min insulin levels increased by 165 pmol/l compared with no changes from baseline of these parameters with placebo added to rosiglitazone (P < 0.001).
  
  
  CONCLUSIONS
  By selectively augmenting early insulin release and decreasing prandial glucose excursions, nateglinide produced a clinically meaningful improvement in overall glycemic exposure in patients with type 2 diabetes inadequately controlled with rosiglitazone. Therefore, nateglinide substantially improves the likelihood of achieving a therapeutic target of HbA(1c) <7.0%.
authors.affiliation: Tulane University Medical Center, New Orleans, Louisiana, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
authors.forename: George
authors.initials: G
authors.lastname: Grunberger
authors.forename: Shamita
authors.initials: S
authors.lastname: Gupta
authors.forename: Sharon
authors.initials: S
authors.lastname: Shen
authors.forename: James E
authors.initials: JE
authors.lastname: Foley
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003510:Cyclohexanes / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004435:Eating / Q000502:physiology*; D005215:Fasting; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010919:Placebos; D000077154:Rosiglitazone; D012449:Safety; D016037:Single-Blind Method; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine; D010919:Placebos; D000077154:Rosiglitazone; D045162:Thiazolidinediones