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GW24-e3085 The dual PPAR alpha/gamma agonist aleglitazar has a beneficial effect on atherogenic dyslipidemia in patients with type 2 diabetes
  1. Matthias Herz1,
  2. Klas Malmberg1,
  3. Markolf Hanefeld2,
  4. A Michael Lincoff3,
  5. Nadejda Mudie1,
  6. Stephen Nicholls4
  1. 1F. Hoffmann-La Roche
  2. 2Center for Clinical Studies, Technical University Dresden, Dresden, Germany
  3. 3Cleveland Clinic, Ohio, USA
  4. 4South Australian Health & Medical Research Institute, University of Adelaide, Adelaide, Australia

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.

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