Improvement of postprandial lipid handling and glucose tolerance in a non-diabetic population by the dual PPARalpha/gamma agonist, tesaglitazar.
This study examined the effect of tesaglitazar (GALIDA), a dual peroxisome proliferator-activated receptor (PPAR)alpha/gamma agonist, on postprandial metabolism. This investigation was part of the Study in Insulin Resistance (SIR) (SH-SBT-0001), a randomised, double-blind, placebo-controlled study that reported improvements in fasting lipid and glucose values with tesaglitazar (0.1, 0.25, 0.5 or 1 mg once daily for 12 weeks) in hypertriglyceridaemic, abdominally obese, non-diabetic patients. A subgroup of 222 patients underwent postprandial lipid and glucose testing at baseline and treatment end. Tesaglitazar 0.25, 0.5 and 1 mg reduced postprandial area under the curve (AUC) for triglycerides by 20% (p=0.003), 30% (p<0.0001) and 41% (p<0.0001), respectively. Free fatty acid (FFA) levels were reduced by 17% with tesaglitazar 0.5 mg (p=0.002) and by 29% with tesaglitazar 1 mg (p<0.0001). Tesaglitazar significantly improved glucose tolerance and increased the proportion of patients with normal glucose tolerance as measured by the oral glucose tolerance test (OGTT). To conclude, postprandial dyslipidaemia and hyperglycaemia, indicators of increased vascular risk, were significantly improved by tesaglitazar treatment in these non-diabetic, hypertriglyceridaemic, abdominally obese subjects.
Fagerberg
Bjorn
B
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, 41345 Göteborg, Sweden. bjorn.fagerberg@wlab.gu.se
Schuster
Herbert
H
Birketvedt
Grethe Støa
GS
Tonstad
Serena
S
Ohman
Karl Peter
KP
Gause-Nilsson
Ingrid
I
D000328:Adult; D000476:Alkanesulfonates / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000494:pharmacology*; D019518:Postprandial Period / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood
D000476:Alkanesulfonates; D001786:Blood Glucose; D008055:Lipids; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; D014280:Triglycerides; C501413:tesaglitazar