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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:416.)
© 2009 American Heart Association, Inc.

Clinical and Population Studies

Effect of Rimonabant on the High-Triglyceride/ Low–HDL-Cholesterol Dyslipidemia, Intraabdominal Adiposity, and Liver Fat

The ADAGIO-Lipids Trial

Jean-Pierre Després; Robert Ross; Gabor Boka; Natalie Alméras; Isabelle Lemieux for the ADAGIO-Lipids Investigators^*

From the Hôpital Laval Research Centre (J.-P.D., N.A., I.L.), Québec, Canada; Queen’s University (R.R.), Kingston, Canada; and sanofi-aventis R&D (G.B.), Antony, France.

Correspondence to Jean-Pierre Després, Québec Heart Institute, Hôpital Laval Research Centre, Université Laval, Quebec, QC, Canada. E-mail jean-pierre.despres{at}crhl.ulaval.ca

Background— Rimonabant, the first selective cannabinoid type 1 (CB₁) receptor antagonist, improves cardiometabolic risk factors in overweight/obese patients. ADAGIO-Lipids assessed the effect of rimonabant on cardiometabolic risk factors and intraabdominal and liver fat.

Methods and Results— 803 abdominally obese patients with atherogenic dyslipidemia (increased triglycerides [TG] or reduced high-density lipoprotein–cholesterol [HDL-C]) were randomized to placebo or rimonabant 20 mg/d for 1 year. HDL-C and TG were coprimary end points. Intraabdominal (visceral) and liver fat were measured by computed tomography in a subgroup of 231 patients. In total, 73% of rimonabant- and 70% of placebo-treated patients completed the study treatment. Rimonabant 20 mg produced significantly greater changes from baseline versus placebo in HDL-C (+7.4%) and TG levels (–18%; P<0.0001), as well as low-density lipoprotein (LDL) and HDL particle sizes, apolipoprotein A1 and B, HDL₂, HDL₃, C-reactive protein, and adiponectin levels (all P<0.05). Rimonabant decreased abdominal subcutaneous adipose tissue (AT) cross-sectional area by 5.1% compared to placebo (P<0.005), with a greater reduction in visceral AT (–10.1% compared to placebo; P<0.0005), thereby reducing the ratio of visceral/subcutaneous AT (P<0.05). Rimonabant significantly reduced liver fat content (liver/spleen attenuation ratio; P<0.005). Systolic (–3.3 mm Hg) and diastolic (–2.4 mm Hg) blood pressure were significantly reduced with rimonabant versus placebo (P<0.0001). The safety profile of rimonabant was consistent with previous studies; gastrointestinal, nervous system, psychiatric, and general adverse events were more common with rimonabant 20 mg.

Conclusions— In abdominally obese patients with atherogenic dyslipidemia, rimonabant 20 mg significantly improved multiple cardiometabolic risk markers and induced significant reductions in both intraabdominal and liver fat.

Key Words: cardiometabolic risk • dyslipidemia • intraabdominal obesity • liver fat • rimonabant

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ADAGIO-Lipids Gives Promises but Faces the Setbacks

Marja-Riitta Taskinen
Arterioscler Thromb Vasc Biol 2009 29: 339-340. [Extract] [Full Text] [PDF]

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