Effect of the administration of a single dose of nateglinide on insulin secretion at two different concentrations of glucose in healthy individuals

Abstract 

Background

Nateglinide is a d-phenylalanine derivative that stimulates fast insulin secretion with a short activity span. It has been suggested that the hypoglycemic effect of nateglinide is related to the glucose concentration, an aspect that still has not been completely evaluated in human beings.

Objective

The aim of this study is to evaluate the effect of nateglinide on the insulin secretion at two different concentrations of glucose level.

Participants and methods

A randomized, double-blind, cross-over, placebo-controlled clinical trial with two parallel groups was carried out; each group was made up by six healthy volunteers who were submitted to a hyperglycemic–hyperinsulinemic clamp technique on two different occasions, one of them prior to the administration of 120 mg nateglinide and the other one prior to the administration of an homologated placebo. One group was submitted to and maintained at a hyperglycemia of 6.9 mmol/l above the fasting glucose level and the other group at a hyperglycemia of 4.1 mmol/l above the baseline of fasting glucose level.

Results

In volunteers submitted to the clamp at 4.1 mmol/l above the baseline of glucose level, the insulin secretion in the early phase was 212.4±55.8 pmol/l in the placebo test versus 338.4±124.8 pmol/l in the nateglinide test (P<.05), whereas in the group submitted at 6.9 mmol/l over the baseline, no significant differences were observed.

Conclusion

Nateglinide increased the early insulin secretion in healthy individuals submitted to a mild hyperglycemia, but not at high glucose concentrations.

Keywords: Nateglinide, Insulin release, Insulin secretion, Insulinotropic effect