Effect of rimonabant on the high-triglyceride/ low-HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat: the ADAGIO-Lipids trial.
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.


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.
Després
Jean-Pierre
JP
Québec Heart Institute, Hôpital Laval Research Centre, Université Laval, Québec, Canada. jean-pierre.despres@crhl.ulaval.ca
Ross
Robert
R
Boka
Gabor
G
Alméras
Natalie
N
Lemieux
Isabelle
I
D052242:Adiponectin / Q000097:blood; D050154:Adiposity / Q000187:drug effects*; D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
C499918:ADIPOQ protein, human; D052242:Adiponectin; D019440:Anti-Obesity Agents; D001053:Apolipoproteins; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D008077:Lipoproteins, LDL; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014280:Triglycerides; D002097:C-Reactive Protein; D000077285:Rimonabant