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, mul-ticentre 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.

Keywords

haemoglobin A1C lipids peroxisome proliferator-activated receptor sulphonylurea tesaglitazar type 2 diabetes mellitus

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