Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycemia and improves overall glycemic control.
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%.
Fonseca
Vivian
V
Tulane University Medical Center, New Orleans, Louisiana, USA.
Grunberger
George
G
Gupta
Shamita
S
Shen
Sharon
S
Foley
James E
JE
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
D001786:Blood Glucose; D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine; D010919:Placebos; D000077154:Rosiglitazone; D045162:Thiazolidinediones