GW24-e3085 The dual PPAR alpha/gamma agonist aleglitazar has a beneficial effect on atherogenic dyslipidemia in patients with type 2 diabetes. (1st October 2013)

• Record Type: Journal Article
• Authors: Herz, Matthias; Malmberg, Klas; Hanefeld, Markolf; Michael Lincoff, A; Mudie, Nadejda; Nicholls, Stephen
• Is Part Of: Heart. Volume 99(2013)Supplement 3
• Page Start: A248
• Page End: A248
• Publication Date: 2013-10-01
• Subjects: Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-2013-304613.699
• Languages: English
• ISSNs: 1355-6037

Abstract

Abstract : Objectives: Dyslipidemia, characterised by increased ratios of triglycerides (TG) and total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C), is a cardiovascular (CV) risk factor in patients with type 2 diabetes (T2D). 1 In addition to evaluating renal effects of aleglitazar in stage 3 chronic kidney disease patients with T2D, this Phase IIb study (AleNephro) assessed effects on CV risk factors, including lipid ratios. Methods: Patients with stage 3 chronic kidney disease and T2D were randomized to 52 weeks' double-blind treatment with aleglitazar 150 μg/d or pioglitazone 45 mg/d, and 8 weeks' follow-up. Secondary/tertiary endpoints included change from baseline in lipid parameters at 52 weeks, and safety and tolerability. Results: Mean % changes in TG/HDL-C and TC/HDL-C ratio at the end of treatment were –41.7 (95% CI: –51.1, –32.4) and –19.8 (95%CI: –24.7, –14.9) with aleglitazar and –17.5 (95% CI: –27.0, –8.0) and –6.6 (95% CI:–11.5, –1.6) with pioglitazone, indicating superior changes with aleglitazar ( P <0.001). Similar reductions were observed in high-sensitivity C-reactive protein (hs-CRP) (–20.2 [95% CI:–37.0, 1.1 for aleglitazar] and –27.8 [95%:–43.0, –8.7] for pioglitazone, P = 0.42). Aleglitazar vs. pioglitazone treatment led to significant improvements in TG (–33.6 [95% CI: –41.1, –26.1] vs. –14.1 [95%CI: –21.7, –6.5]; P < 0.001), HDL-C (22.0 [95% CI: 17.4, 26.6] vs. 11.6 [95% CI: 6.9, 16.3]; P < 0.001), low density lipoprotein cholesterol (LDL-C) (–7.3 [95% CI:–13.2, –1.0] vs. –0.3 [95%CI: –6.8, 6.6]; P = 0.039), non-HDL-C (–13.1 [95% CI: –19.1, –7.0] vs. –2.2 [95% CI: –8.3, 4.0]; P < 0.001) and TC (–4.6 [95% CI: –9.2, 0.0] vs. 0.7 [95%CI: –4.0, 5.4], P = 0.03). Data for hs-CRP and LDL-C were log-transformed. Conclusions: The observed favourable change in diabetic dyslipidemia may potentially have beneficial effects on CV risk in patients with T2D, which is currently tested in the Phase III AleCardio outcomes trial.