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

Tools

Item Type:	Article
Title:	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
Creators Name:	Fagerberg, B., Edwards, S., Halmos, T., Lopatynski, J., Schuster, H., Stender, S., Stoa-Birketvedt, G., Tonstad, S., Halldorsdottir, S. and Gause-Nilsson, I.
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 α/γ 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.
Keywords:	Cardiovascular risk factors, Dyslipidaemia, HDL-cholesterol, Hyperinsulinaemia, Hypoglycaemic agents, Insulin resistance, LDL-cholesterol, Peroxisome proliferator-activated receptor, Triglycerides
Source:	Diabetologia
ISSN:	0012-186X
Volume:	48
Page Range:	1716-1725
Date:	7 July 2005
Official Publication:	https://doi.org/10.1007/s00125-005-1846-8
PubMed:	View item in PubMed

Repository Staff Only: item control page