Nateglinide Improves Early Insulin Secretion and Controls Postprandial Glucose Excursions in a Prediabetic Population
- Carola Saloranta, MD1,
- Christiane Guitard, MD2,
- Eckhard Pecher, MSC2,
- Pedro de Pablos-Velasco, MD3,
- Kaj Lahti, MD4,
- Patrick Brunel, MD2 and
- Leif Groop, MD5
- 1Helsinki University Hospital, Department of Medicine, Helsinki, Finland
- 2Novartis Pharma, AG, Basel, Switzerland
- 3University of Las Palmas de Gran Canaria, Faculty of Medicine, Las Palmas, Canary Islands, Spain
- 4Primary Health Care Center, Vaasa, Finland
- 5Department of Endocrinology, University of Lund, Malmo, Sweden
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.
RESEARCH DESIGN AND 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 ≤3.3 mmol/l (plasma glucose ≤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.
- AE, adverse event
- AUC, area under the curve
- DCCT, Diabetes Control and Complications Trial
- FPG, fasting plasma glucose
- IGT, impaired glucose tolerance
- IRI, immunoreative insulin
- OGTT, oral glucose tolerance test
- SAE, serious AE
- SMBG, self-monitoring of blood glucose
- SU, sulfonylurea
- UKPDS, U.K. Prospective Diabetes Study
- ULN, upper limit of normal
Footnotes
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Address correspondence and reprint requests to Christiane Guitard, Clinical Research, Novartis Pharma, AG, CH-4002, Basel, Switzerland. E-mail: christiane.guitard{at}pharma.novartis.com.
Received for publication 4 April 2002 and accepted in revised form 11 September 2002.
C.G. and E.P. hold stock in, C.S. has received funds from, and P.d.P.-V. has received honoraria from Novartis.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE
