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