Effects of the new oral hypoglycaemic agent nateglinide on insulin secretion in Type 2 diabetes mellitus

Diabet Med. 2000 Mar;17(3):225-9. doi: 10.1046/j.1464-5491.2000.00256.x.


Aims: The new non-sulphonylurea oral hypoglycaemic agent nateglinide has been shown to enhance insulin secretion in animals and in healthy human volunteers and thus offers a potential advance in the treatment of Type 2 diabetes mellitus. This study examined whether nateglinide can enhance insulin secretion, and particularly the first phase insulin response, in patients with Type 2 diabetes.

Methods: A double-blind, placebo-controlled trial, examining the effects of a single oral dose of 60 mg nateglinide, given 20 min prior to an intravenous glucose tolerance test (IGTT), on insulin secretion in 10 otherwise healthy Caucasian men with recently diagnosed Type 2 diabetes (duration since diagnosis 0-44 months).

Results: Insulin secretion (both overall and first phase) was significantly increased by nateglinide (P < 0.001), as were C-peptide (P < 0.001) and proinsulin (P < 0.001) secretion. Overall glucose concentrations following glucose challenge were lower after nateglinide than after placebo (P = 0.05).

Conclusions: Nateglinide significantly increases insulin secretion in Type 2 diabetic patients, in particular restoring the first phase insulin response. Further study is necessary to determine the effects of chronic administration on insulin secretion and blood glucose concentration.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • C-Peptide / metabolism
  • Cyclohexanes / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Kinetics
  • Male
  • Middle Aged
  • Nateglinide
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / therapeutic use
  • Placebos
  • Proinsulin / metabolism


  • Blood Glucose
  • C-Peptide
  • Cyclohexanes
  • Hypoglycemic Agents
  • Insulin
  • Placebos
  • Nateglinide
  • Phenylalanine
  • Proinsulin