New Dual TZD Results Promising

Investigators were cautious in interpreting the findings, however, given that other PPAR agonists have not reached market because of safety concerns, including muraglitazar, which increased the risk of cardiovascular events; they emphasize that no clinically applicable conclusions can be based on the findings.

 

“However, the significant change in lipids and glycemic end points coupled with the favorable safety profile represent promising data for aleglitazar and provide good evidence to enter phase 3 clinical investigation,” writes lead investigator Dr. Robert Henry, University of California, San Diego.

 

In the trial, known as SYNCHRONY, 332 patients with Type 2 diabetes were randomized to treatment with aleglitazar 50, 150, 300, 600 µg or matching placebo or to pioglitazone 45 mg once daily as a reference. The drug reduced baseline HbA_1c levels versus placebo in a dose-dependent manner, ranging from a reduction of 0.36% with 50 µg to 1.35% at the 600-µg dose.

 

Edema, hemodilution, and weight gain also occurred in a dose-dependent manner, but doses less than 300 µg were well tolerated, with no patients developing congestive heart failure and fewer patients developing edema than those treated with placebo or pioglitazone. Maximum reductions in triglycerides, a 43% decrease, as well as maximum increases in HDL cholesterol, 20%, occurred with the 150-µg dose of aleglitazar.

 

In an editorial, Dr. Bernard Charbonnel, University of Nantes, France, cautions that even muraglitazar showed positive effects on lipids and blood glucose levels, and while these findings are encouraging, “it is impossible to draw definitive clinical conclusions from such a phase 2 study.”