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

Abstract

This randomised, double-blind, parallel-group, multicentre study investigated the effects of the dual peroxisome proliferator-activated receptor (PPAR) α/γ 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 (HbA 1C) 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.