MONDAY, March 26 (HealthDay News) -- LY518674, an investigational peroxisome proliferator-activated receptor (PPAR) alpha agonist, improves lipid levels but may not be safe, according to the results of a study published online March 25 in the Journal of the American Medical Association to coincide with the American College of Cardiology's annual conference in New Orleans.
Steven E. Nissen, M.D., of the Cleveland Clinic Foundation in Ohio, and colleagues conducted two trials, the first of which randomized 309 patients with atherogenic dyslipidemia to receive LY518674, fenofibrate or placebo. In the second study, they randomized 304 patients with hypercholesterolemia to receive atorvastatin or placebo for four weeks, followed by LY518674 or placebo for 12 more weeks.
In both studies, the researchers found that LY518674 significantly reduced triglyceride levels and increased high-density lipoprotein cholesterol levels. But the studies raised safety concerns as both LY518674 and fenofibrate increased serum creatinine levels in some patients, although there were no cases of rhabdomyolysis or acute renal failure. In addition, LY518674 increased LDL-C and Apo A-II.
"The results of this pair of trials demonstrate the challenges in developing new PPAR agonists as therapeutic agents. These drugs modulate activity of a large number of genes, some of which produce unknown effects," the authors write. "Accordingly, the beneficial effects of PPAR activation appear to be associated with a variety of untoward effects, which may include oncogenesis, renal dysfunction, rhabdomyolysis, and cardiovascular toxicity."
The study was funded by Eli Lilly and Co.
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