• Robert R Henry, A Michael Lincoff, Sunder Mudaliar, Michael Rabbia, Cathy Chognot, and Matthias Herz.
• Department of Medicine, University of California at San Diego and VA San Diego Healthcare System, San Diego, CA 92161, USA. rrhenry@ucsd.edu
• Lancet. 2009 Jul 11;374(9684):126-35.

BackgroundDespite previous reports of potential adverse cardiovascular effects of peroxisome proliferator-activated receptor (PPAR) agonists, the promise for PPAR agonists to positively affect risk of cardiovascular disease in patients with type 2 diabetes is of continued interest. The SYNCHRONY study aimed to establish the glucose-lowering and lipid-modifying effects, and safety profile, of the dual PPAR-alpha and PPAR-gamma agonist aleglitazar.MethodsIn this double-blind study, patients with type 2 diabetes (either drug-naive or pre-treated with ClinicalTrials.gov, number NCT00388518.FindingsThe efficacy analysis excluded six patients (n=0 in pioglitazone group; n=1 in each of placebo, 50 mug, 150 mug, and 600 mug aleglitazar groups; and n=2 in 300 mug aleglitazar group). Aleglitazar significantly reduced baseline HbA(1c) versus placebo in a dose-dependent manner, from -0.36% (95% CI 0.00 to -0.70, p=0.048) with 50 mug to -1.35% (-0.99 to -1.70, p<0.0001) with 600 mug. The trend of changes over time suggests that the maximum effect of aleglitazar on HbA(1c) concentration was not yet reached after 16 weeks of treatment. Oedema, haemodilution, and weight gain occurred in a dose-dependent manner. However, at aleglitazar doses less than 300 mug, no patients had congestive heart failure, frequency of oedema was similar to placebo (one case at 50 mug, two at 150 mug, and three with placebo) and less than with pioglitazone (four cases), and bodyweight gain was less than with pioglitazone (0.52 kg at 150 mug vs 1.06 kg).InterpretationThe favourable balance in the safety and efficacy profile of aleglitazar represents encouraging short-term clinical data for this agent and provides good evidence to enter phase III investigation.FundingF Hoffmann-La Roche AG (Switzerland).

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