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Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor α/γ agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome.

Hansen BC, Tigno XT, Bénardeau A, Meyer M, Sebokova E, Mizrahi J - Cardiovasc Diabetol (2011)

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine and Pediatrics, University of South Florida, Tampa, FL, USA. bchansen@aol.com

ABSTRACT

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.

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Related in: MedlinePlus

Individual levels of A) low-density lipoprotein cholesterol, B) apolipoprotein B, C) very low-density lipoprotein cholesterol, and D) apolipoprotein C-III in monkeys given aleglitazar 0.03 mg/kg per day. The final day of dosing at 0.03 mg/kg per day aleglitazar (labeled in the figures as day 42), due to scheduling needs, ranged across monkeys from 44 to 46 days.
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Figure 4: Individual levels of A) low-density lipoprotein cholesterol, B) apolipoprotein B, C) very low-density lipoprotein cholesterol, and D) apolipoprotein C-III in monkeys given aleglitazar 0.03 mg/kg per day. The final day of dosing at 0.03 mg/kg per day aleglitazar (labeled in the figures as day 42), due to scheduling needs, ranged across monkeys from 44 to 46 days.

Mentions: Aleglitazar decreased TG levels in all monkeys by an average of 89% (328 to 36 mg/dL; P = 0.057) with 0.03 mg/kg per day (Figure 3A). Upon statistical normalization of the TG levels using logarithmic transformation, due to the wide baseline range (Figure 3A), a highly significant decrease was observed following administration of aleglitazar (Figure 3B; P = 0.0048). Total HDL-C levels increased by 125% (46 to 102 mg/dL) with aleglitazar (P = 0.0007; Figure 3C). LDL-C concentrations declined significantly by 41% with aleglitazar (92 to 54 mg/dL; P = 0.015; Figure 4A). Treatment with aleglitazar slightly increased the mean levels of apolipoprotein A-I (17% increase; P = 0.096; Figure 3D) and apolipoprotein A-II (17% increase; P = 0.111).


Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor α/γ agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome.

Hansen BC, Tigno XT, Bénardeau A, Meyer M, Sebokova E, Mizrahi J - Cardiovasc Diabetol (2011)

Individual levels of A) low-density lipoprotein cholesterol, B) apolipoprotein B, C) very low-density lipoprotein cholesterol, and D) apolipoprotein C-III in monkeys given aleglitazar 0.03 mg/kg per day. The final day of dosing at 0.03 mg/kg per day aleglitazar (labeled in the figures as day 42), due to scheduling needs, ranged across monkeys from 44 to 46 days.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037308&req=5

Figure 4: Individual levels of A) low-density lipoprotein cholesterol, B) apolipoprotein B, C) very low-density lipoprotein cholesterol, and D) apolipoprotein C-III in monkeys given aleglitazar 0.03 mg/kg per day. The final day of dosing at 0.03 mg/kg per day aleglitazar (labeled in the figures as day 42), due to scheduling needs, ranged across monkeys from 44 to 46 days.
Mentions: Aleglitazar decreased TG levels in all monkeys by an average of 89% (328 to 36 mg/dL; P = 0.057) with 0.03 mg/kg per day (Figure 3A). Upon statistical normalization of the TG levels using logarithmic transformation, due to the wide baseline range (Figure 3A), a highly significant decrease was observed following administration of aleglitazar (Figure 3B; P = 0.0048). Total HDL-C levels increased by 125% (46 to 102 mg/dL) with aleglitazar (P = 0.0007; Figure 3C). LDL-C concentrations declined significantly by 41% with aleglitazar (92 to 54 mg/dL; P = 0.015; Figure 4A). Treatment with aleglitazar slightly increased the mean levels of apolipoprotein A-I (17% increase; P = 0.096; Figure 3D) and apolipoprotein A-II (17% increase; P = 0.111).

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine and Pediatrics, University of South Florida, Tampa, FL, USA. bchansen@aol.com

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus