Addition of Nateglinide to Rosiglitazone Monotherapy Suppresses Mealtime Hyperglycemia and Improves Overall Glycemic Control
- Vivian Fonseca, MD1,
- George Grunberger, MD2,
- Shamita Gupta, PHARMD3,
- Sharon Shen, MS3 and
- James E. Foley, PHD3
- 1Tulane University Medical Center, New Orleans, Louisiana
- 2Grunberger Diabetes Institute, Bloomfield Hills, Michigan
- 3Novartis Pharmaceuticals, East Hanover, New Jersey
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.
RESEARCH DESIGN AND 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 HbA1c between 7 and 11% (inclusive). Efficacy parameters tested included HbA1c 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, HbA1c did not change (Δ = 0.0 ± 0.1%). In patients randomized to nateglinide, HbA1c decreased from 8.3 to 7.5% (Δ = −0.8 ± 0.1%, P < 0.0001 vs. placebo). Target HbA1c (<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 HbA1c <7.0%.
- AE, adverse event
- AUC, area under the curve
- CHF, congestive heart failure
- FPG, fasting plasma glucose
- HOMA, homeostasis model assessment
- ITT, intent to treat
- PPG, postprandial glucose
- SAE, serious adverse event
- TZD, thiazolidinedione
Footnotes
-
Address correspondence and reprint requests to James E. Foley, PhD, Novartis Pharmaceuticals Corp., One Healthcare Plaza, East Hanover, NJ 07936. E-mail: james.foley{at}pharma.novartis.com.
Received for publication 11 November 2002 and accepted in revised form 20 February 2003.
V.F. received a grant from Tulane University Medical Center to conduct this study. V.F. and G.G. have received funding for this and other studies from Novartis Pharmaceuticals, which manufactures and markets nateglinide.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE
