Effects of a new oral hypoglycaemic agent (CS-045) on metabolic abnormalities and insulin resistance in type 2 diabetes

Diabet Med. Aug-Sep 1994;11(7):685-91. doi: 10.1111/j.1464-5491.1994.tb00333.x.

Abstract

The effects of a thiazolidinedione antidiabetic agent (CS-045) on diabetic metabolic abnormalities were studied in a double-blind clinical trial. Fourteen patients with Type 2 diabetes were selected according to study criteria. Eight were treated with oral CS-045 at 400 mg daily, and six were given placebo. A multi-step, hyperinsulinaemic, euglycaemic clamp study, with simultaneous plasma free fatty acid study, and glucagon tolerance test were performed before and after administration of drug. Following 3 months of treatment with CS-045, there were significant decreases in the mean levels of fasting plasma glucose (from 9.18 +/- 0.95 to 7.78 +/- 0.44 mmol l-1), postprandial plasma glucose (from 11.8 +/- 1.23 to 10.36 +/- 1.06 mmol l-1), and haemoglobin A1c (from 9.3 +/- 0.4 to 6.8 +/- 0.4%). Insulin sensitivity also improved (1st step: from 3.12 +/- 0.33 to 4.70 +/- 0.47 mg kg-1 min-1 (p < 0.01); 2nd step: from 5.61 +/- 0.63 to 7.54 +/- 0.58 mg kg-1 min-1 (p < 0.01); 3rd step: from 9.21 +/- 0.67 to 11.10 +/- 0.87 mg kg-1 min-1). The fasting free fatty acid level decreased significantly from 0.28 +/- 0.04 to 0.22 +/- 0.02 g l-1. The residual free fatty acid level (%) under insulin infusion clamp conditions decreased significantly from 63.7 +/- 9.7 to 45.0 +/- 9.2%. CS-045 treatment was associated with decrease in total cholesterol, total triglycerides, and increase in HDL cholesterol. Basal C-peptide immunoreactivity level decreased, but there was no change in the peak C-peptide immunoreactivity value.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Chromans / pharmacology
  • Chromans / therapeutic use*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Fatty Acids, Nonesterified / blood
  • Glucagon
  • Glucose Clamp Technique
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin Resistance*
  • Middle Aged
  • Placebos
  • Reference Values
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*
  • Thiazolidinediones*
  • Troglitazone

Substances

  • Blood Glucose
  • Chromans
  • Fatty Acids, Nonesterified
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Placebos
  • Thiazoles
  • Thiazolidinediones
  • Glucagon
  • Troglitazone