Abstract 849: Aleglitazar, a Balanced Peroxisome Proliferator-Activated Receptor (PPAR)α/γ Agonist, Provides Beneficial Effects on Cardiovascular Markers of Inflammation and Clotting
Aleglitazar (ALE) is a balanced dual PPARα/γ agonist, designed to optimize glycemic and lipid benefits, and minimize PPAR-related adverse effects, including weight gain, and peripheral edema. The SYNCHRONY study demonstrated significant improvements in glycemic control and lipids with a 150 μg dose of ALE in patients with type 2 diabetes (T2D), with no evidence of adverse cardiovascular safety. The current exploratory analysis of SYNCHRONY investigated the effects of ALE at a range of doses on cardiovascular markers, including high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), and fibrinogen. Following a 4- to 5-week placebo run-in period, 332 patients (drug-naïve or pretreated with ≤2 oral antidiabetic agents) were randomized to 16 weeks’ double-blind treatment with ALE at 1 of 4 daily doses (50, 150, 300 or 600 μg) or placebo, or to open-label pioglitazone (PIO) 45 mg/day. After 16 weeks’ treatment, a trend towards reduction in hsCRP was observed with ALE vs placebo, which appeared to be dose dependent. Reductions from baseline in hsCRP were similar for the ALE 150 μg dose and 45 mg of PIO. Reductions from baseline in PAI-1 were significant vs placebo at the 300 and 600 μg doses of ALE, and were numerically greater than with PIO, but not with the 150 μg dose. Dose-dependent reductions from baseline fibrinogen were observed for ALE that were significant vs placebo at doses ≥150 μg. The expected PPARγ effects on body weight and fluid retention were observed with ALE, but at the 150 μg dose body weight gain was less than with PIO (0.52 vs 1.06 kg) and incidence of peripheral edema (2 cases) was similar to placebo (3 cases) and less than with PIO (4 cases).