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.

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 < 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: Carola Saloranta, Christiane Guitard, Eckhard Pecher, Pedro De Pablos-Velasco, Kaj Lahti, Patrick Brunel, Leif Groop
• Journal: Diabetes care (Diabetes Care) Vol. 25 Issue 12 Pg. 2141-6 (Dec 2002) ISSN: 0149-5992 [Print] United States
• PMID: 12453951 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Blood Glucose
• Cyclohexanes
• Hypoglycemic Agents
• Insulin
• Nateglinide
• Phenylalanine

Topics

• Adult
• Aged
• Blood Glucose (drug effects, metabolism)
• Body Mass Index
• Cyclohexanes (therapeutic use)
• Double-Blind Method
• Female
• Glucose Tolerance Test
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (blood, metabolism)
• Insulin Secretion
• Male
• Middle Aged
• Nateglinide
• Phenylalanine (analogs & derivatives, therapeutic use)
• Postprandial Period
• Prediabetic State (blood, drug therapy)