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

John PH Wilding

University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK.

Ingrid Gause-Nilsson

AstraZeneca R&D, Mölndal, Sweden.

Anders Persson

AstraZeneca R&D, Mölndal, Sweden.

This randomised, double-blind, parallel-group, mul-ticentre 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.

Key Words: haemoglobin A1C • lipids • peroxisome proliferator-activated receptor • sulphonylurea • tesaglitazar • type 2 diabetes mellitus

Diabetes and Vascular Disease Research, Vol. 4, No. 3, 194-203 (2007)
DOI: 10.3132/dvdr.2007.040
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