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"We know that the most prevalent form of the metabolic syndrome isassociated with abdominal obesity, particularly with an excess of visceralfat as well as with accumulation of fat at undesired sites such as the liver,the heart, the muscle and the pancreas, a phenomenon referred to as ectopicfat deposition" mentioned Dr Jean-Pierre Despres from the Hopital LavalResearch Center, Universite Laval, Quebec, CANADA, who is the principalinvestigator of ADAGIO LIPIDS. "Although we had evidence from the phase IIIstudies conducted with rimonabant that antagonism of the endocannabinoidsystem could induce a reduction in waist circumference (a crude marker ofabdominal fat) and improve several features of the metabolic syndrome, nostudy had ever quantified the effect of this drug on visceral adiposity andliver fat" he added.
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ADAGIO-LIPIDS was a study conducted in 799 patients with abdominalobesity and with the high triglyceride - low HDL-cholesterol dyslipidemia.Patients were randomized to moderate caloric restriction (600 kcal/day) witheither a placebo or rimonabant (20mg/day). First, results confirmed theconsistent effects of rimonabant on several markers of cardiometabolic risk.For instance, HDL-cholesterol was increased by 7.4% with rimonabant comparedto placebo (p<0.0001) whereas triglyceride levels were reduced by 18% withrimonabant compared to placebo (p<0.0001). Whereas rimonabant had no effecton LDL-cholesterol levels, the drug induced a major shift in the distributionof the size of LDL particles with a substantial reduction in the proportionof small, atherogenic LDL (decrease of 6.5% vs placebo, p<0.0001) and aconcomitant increase in the concentration of large LDL particles (increase of4.8% vs placebo). Several markers of HDL concentration and quality were alsoimproved with rimonabant compared to placebo including an increase in apo A-I(+3.2% vs placebo, p=0.02), HDL particle size (+0.9% vs placebo, p<0.001) andan increase in levels of both HDL2 (+52.6% vs placebo, p<0.03) and HDL3(+4.3% vs placebo, p<0.01) subfractions. Apo B was also significantly reduced(-4.4% vs placebo, p<0.01) leading to a decrease in the apo B/apo A-I ratio(p<0.0001). Inflammation was also improved as revealed by a 17% reduction inCRP levels compared to placebo (p<0.01) whereas there was a very significantincrease in the blood concentration of an important adipose tissue-derivedcytokine, adiponectin, which increased by 18.9% compared to placebo(p<0.0001).
"Results of ADAGIO-LIPIDS are pretty much "textbook" regarding what weknew from endocannabinoid physiology and their effect on lipid metabolism"mentioned Dr Despres. "All markers of cardiometabolic risk improved in theright direction with rimonabant therapy, including a significant reduction of-3.3 mmHg for systolic and of -2.4 mmHg for diastolic blood pressure(p<0.0001). The next important question was, how does rimonabant work?"
"Results of the CT imaging study are pretty straightforward. We foundthat rimonabant therapy for one year induced a preferential mobilization ofvisceral adipose tissue compared to placebo (reduction of 10.1% vs placebo,p<0.0005), which was greater that the loss of subcutaneous fat (decrease of5.1% vs placebo, p<0.005)" stated Dr Robert Ross, the co-principalinvestigator of ADAGIO-LIPIDS. "Another relevant finding is that we reportfor the fir
