Tesaglitazar, as add-on therapy to sulphonylurea, dose-dependently improves glucose and lipid abnormalities in patients with type 2 diabetes

Diab Vasc Dis Res. 2007 Sep;4(3):194-203. doi: 10.3132/dvdr.2007.040.

Abstract

This randomised, double-blind, parallel-group, multicentre study investigated the effects of the dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, tesaglitazar (0.5 and 1 mg), as add-on treatment in 568 patients with type 2 diabetes that was poorly controlled with sulphonylurea therapy titrated to the highest tolerated dose. There was a significant placebo-corrected reduction in glycosylated haemoglobin (HbA1C) from baseline to week 24 with tesaglitazar 0.5 mg and 1 mg (mean [95% confidence interval]: -0.93% [-1.09, -0.77] and -1.3% [-1.46, -1.14]; p<0.0001). Significant reductions were observed in insulin, fasting plasma glucose (FPG), triglyceride (all p<0.001) and non-high-density lipoprotein (HDL) cholesterol (p<0.001). Tesaglitazar increased levels of HDL-cholesterol (p<0.0001), adiponectin (p<0.0001) and leptin (p<0.001), but was associated with dose-dependent increases in serum creatinine and decreases in haemoglobin. This study showed improvements in glycaemic control and dyslipidaemia in patients with type 2 diabetes poorly controlled with existing sulphonylurea therapy. Although tesaglitazar has now been discontinued from clinical development, these results remain relevant to future research into PPAR agonists.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alkanesulfonates / pharmacology
  • Alkanesulfonates / therapeutic use*
  • Blood Glucose / drug effects*
  • Cholesterol, HDL / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Lipids / blood*
  • Male
  • Middle Aged
  • PPAR alpha / agonists*
  • PPAR gamma / agonists*
  • Phenylpropionates / pharmacology
  • Phenylpropionates / therapeutic use*
  • Sulfonylurea Compounds / pharmacology
  • Sulfonylurea Compounds / therapeutic use*

Substances

  • Alkanesulfonates
  • Blood Glucose
  • Cholesterol, HDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • PPAR alpha
  • PPAR gamma
  • Phenylpropionates
  • Sulfonylurea Compounds
  • tesaglitazar