Individual and combined effects of peroxisome proliferator-activated receptor and {gamma} agonists, fenofibrate and rosiglitazone, on biomarkers of lipid and glucose metabolism in healthy nondiabetic volunteers.
This open-label, randomized, placebo-controlled, incomplete-block, 3-period crossover pilot study investigated the effects of peroxisome proliferator-activated receptor alpha- and gamma-agonists on biomarkers of lipid and glucose metabolism in 12 nondiabetic subjects. Plasma samples were collected before and after each 14-day treatment with placebo, fenofibrate (201 mg/d), rosiglitazone (4 mg twice daily), and combined fenofibrate (201 mg/d) plus rosiglitazone (4 mg twice daily). Except for triglycerides (P < .042) and free fatty acids (P < .074), no significant interaction was demonstrated between fenofibrate and rosiglitazone; thus, the effect due to each drug alone was evaluated (presence/absence of drug). Fenofibrate significantly (P < .050) increased lipoprotein lipase activity (35%) and decreased apolipoproteins B (13%) and C-III (20%). Rosiglitazone significantly (P < .050) decreased fasting glucose (7.3%) and increased apolipoprotein C-III (19%) and adiponectin (137%). Fenofibrate and rosiglitazone also produced effects on triglycerides and free fatty acids, but it was not possible to determine if these effects were synergistic in nature.
Wagner
J A
JA
Department of Clinical Pharmacology, Merck Research Laboratories, 126 East Lincoln Avenue, P.O. Box 2000, RY34-A548, Rahway, NJ 07065, USA.
Larson
P J
PJ
Weiss
S
S
Miller
J L
JL
Doebber
T W
TW
Wu
M S
MS
Moller
D E
DE
Gottesdiener
K M
KM
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D004347:Drug Interactions; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood*; D008297:Male; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010865:Pilot Projects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D015415:Biomarkers; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D008055:Lipids; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011345:Fenofibrate