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Tesaglitazar, a Novel Dual Peroxisome Proliferator-Activated Receptor alpha/gamma Agonist, Dose-Dependently Improves the Metabolic Abnormalities Associated With Insulin Resistance in a Non-Diabetic Population

Tesaglitazar, a Novel Dual Peroxisome Proliferator-Activated Receptor alpha/gamma Agonist, Dose-Dependently Improves the Metabolic Abnormalities Associated With Insulin Resistance in a Non-Diabetic Population

B Fagerberg, S Edwards, T Halmos, J Lopatynski, H Schuster, S Stender, G Stoa-Birketvedt, S Tonstad, S Halldórsdóttir, I Gause-Nilsson

Diabetologia. 2005 Sep;48(9):1716-25.

PMID: 16001233

Abstract:

Aims/hypothesis:
Insulin resistance is associated with abnormalities in lipid and glucose metabolism, which are major components of metabolic syndrome and risk factors for vascular disease. This study examined the effect of tesaglitazar (Galida), a novel, dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, on lipid and glucose metabolism in patients with evidence of insulin resistance.
Methods:
A 12-week, multicentre, randomised, double-blind, placebo-controlled, dose-finding study compared the efficacy and safety of oral tesaglitazar (0.1, 0.25, 0.5 and 1.0 mg/day) and placebo in 390 non-diabetic patients with hypertriglyceridaemia (plasma triglyceride concentration >1.7 mmol/l) and abdominal obesity (waist-to-hip ratio >0.90 for men and >0.85 for women).
Results:
A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the primary endpoint) by 37% (95% CI: -43% to -30%; p<0.0001), non-HDL-cholesterol by 15% (95% CI: -20% to -10%; p<0.0001) and NEFA by 40% (95% CI: -51% to -27%; p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to -24%; p<0.0001). At the end of treatment there was a dose-dependent increase in patients with pattern A LDL particle diameter (40% at baseline vs 87% at 12 weeks for tesaglitazar 1.0 mg). Tesaglitazar produced significant reductions in fasting insulin concentration (-35%; p<0.0001) and plasma glucose concentration (-0.47 mmol/l; p<0.0001). Respiratory infection and gastrointestinal symptoms were the most common adverse events and were similarly frequent in all groups.
Conclusions/interpretation:
Tesaglitazar was well tolerated and produced significant, dose-dependent improvements in lipid and glucose metabolism and insulin sensitivity. Tesaglitazar may have the potential to prevent vascular complications and delay progression to diabetes in these patients.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP251565852	Tesaglitazar		251565-85-2	Price

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