BACKGROUND: Glycemic control and management of dyslipidemia to reduce 
cardiovascular risk are major therapeutic goals in individuals with type 2 
diabetes mellitus (T2DM). This study was performed to evaluate the effects of 
aleglitazar, a balanced dual peroxisome proliferator-activated receptor α/γ 
(PPARα/γ) agonist, on both lipid and glycemic parameters in obese, 
hypertriglyceridemic, insulin-resistant rhesus monkeys.
METHODS: A 135-day efficacy study was performed in six rhesus monkeys. After a 
28-day baseline assessment (vehicle only), monkeys received oral aleglitazar 
0.03 mg/kg per day for 42 days, followed by a 63-day washout period. Plasma 
levels of markers of glycemic and lipid regulation were measured at baseline, at 
the end of the dosing period, and at the end of the washout period.
RESULTS: Compared with baseline values, aleglitazar 0.03 mg/kg per day reduced 
triglyceride levels by an average of 89% (328 to 36 mg/dL; P = 0.0035 when 
normalized for baseline levels) and increased high-density lipoprotein 
cholesterol levels by 125% (46 to 102 mg/dL; P = 0.0007). Furthermore, 
aleglitazar reduced low-density lipoprotein cholesterol levels (41%) and 
increased levels of apolipoprotein A-I (17%) and A-II (17%). Aleglitazar also 
improved insulin sensitivity by 60% (P = 0.001). Mean body weight was reduced by 
5.9% from baseline values with aleglitazar at this dose (P = 0.043).
CONCLUSIONS: Aleglitazar, a dual PPARα/γ agonist, has beneficial effects on both 
lipid and glucose parameters and may have a therapeutic role in modifying 
cardiovascular risk factors and improving glycemic control in patients with 
T2DM.