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Hopital Laval

Imaging Results From the ADAGIO-LIPIDS Reveal That Effects of Rimonabant on Cardiometabolic Risk Profile Include Loss of Visceral Fat and Mobilization of Liver Fat

Quebec City, Canada (ots/PRNewswire)

At a late breaking
presentation made on April 29th during the Annual meeting of the
European Atherosclerosis Society held in Istanbul, the investigators
of ADAGIO-LIPIDS presented the key findings of a one year trial
aiming at further studying the effects of rimonabant on several
features of HDL and on a comprehensive set of cardiometabolic
markers. Furthermore, an imaging substudy using computed tomography
was conducted to test, for the first time, the hypothesis that
rimonabant could induce a loss of visceral fat and liver fat.
"We know that the most prevalent form of the metabolic syndrome
is associated with abdominal obesity, particularly with an excess of
visceral fat 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 ectopic fat deposition" mentioned Dr
Jean-Pierre Despres from the Hopital Laval Research Center,
Universite Laval, Quebec, CANADA, who is the principal investigator
of ADAGIO LIPIDS. "Although we had evidence from the phase III
studies conducted with rimonabant that antagonism of the
endocannabinoid system could induce a reduction in waist
circumference (a crude marker of abdominal fat) and improve several
features of the metabolic syndrome, no study had ever quantified the
effect of this drug on visceral adiposity and liver fat" he added.
ADAGIO-LIPIDS was a study conducted in 799 patients with
abdominal obesity and with the high triglyceride - low
HDL-cholesterol dyslipidemia. Patients were randomized to moderate
caloric restriction (600 kcal/day) with either a placebo or
rimonabant (20mg/day). First, results confirmed the consistent
effects of rimonabant on several markers of cardiometabolic risk. For
instance, HDL-cholesterol was increased by 7.4% with rimonabant
compared to placebo (p<0.0001) whereas triglyceride levels were
reduced by 18% with rimonabant compared to placebo (p<0.0001).
Whereas rimonabant had no effect on LDL-cholesterol levels, the drug
induced a major shift in the distribution of the size of LDL
particles with a substantial reduction in the proportion of small,
atherogenic LDL (decrease of 6.5% vs placebo, p<0.0001) and a
concomitant increase in the concentration of large LDL particles
(increase of 4.8% vs placebo). Several markers of HDL concentration
and quality were also improved 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) and an 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 in CRP levels compared to placebo (p<0.01) whereas there
was a very significant increase in the blood concentration of an
important adipose tissue-derived cytokine, adiponectin, which
increased by 18.9% compared to placebo (p<0.0001).
"Results of ADAGIO-LIPIDS are pretty much "textbook" regarding
what we knew from endocannabinoid physiology and their effect on
lipid metabolism" mentioned Dr Despres. "All markers of
cardiometabolic risk improved in the right 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
found that rimonabant therapy for one year induced a preferential
mobilization of visceral adipose tissue compared to placebo
(reduction of 10.1% vs placebo, p<0.0005), which was greater that the
loss of subcutaneous fat (decrease of 5.1% vs placebo, p<0.005)"
stated Dr Robert Ross, the co-principal investigator of
ADAGIO-LIPIDS. "Another relevant finding is that we report for the
first time that rimonabant induced a significant mobilization of
liver fat (decrease in the fatty liver index, p<0.005) which was
associated with a significant improvement in ALT levels (p<0.001), a
commonly used marker of liver function also associated with the
features of the metabolic syndrome" he added.
As CB1 receptors are located in organs other than the brain, such
as the adipose tissue and the liver, results of ADAGIO-LIPIDS are
consistent with the hypothesis that antagonism of the these
peripheral CB1 receptors could slow lipogenesis in both adipose
tissue and the liver, leading to loss of both visceral and liver fat.
Regarding safety, as patients previously treated for symptoms of
depression were excluded from the ADAGIO-LIPIDS trial, the incidence
of side effects leading to discontinuation was essentially similar to
the previously published phase III studies. "These results provide
further evidence of the acceptable safety profile of rimonabant
provided that the drug is used as currently recommended in clinical
practice. Patients with a history of depression or on
anti-depressants should not be treated with rimonabant." emphasized
Dr Despres.
"As we now have evidence that patients with visceral obesity
represent the subgroup of overweight/obese patients with an activated
endocannabinoid system, results of ADAGIO-LIPIDS provide support to
the notion that patients with visceral obesity who are often either
dyslipidemic or with type 2 diabetes (or both) represent a relevant
subpopulation of overweight/obese patients who would particularly
benefit from rimonabant therapy" jointly concluded Dr Despres and
About Hopital Laval
Founded in 1918, Hopital Laval is the heart and lung institute of
Universite Laval. It provides the population of Central and Eastern
Quebec with subspecialized care and services in cardiology,
pneumology, and the surgical management of obesity. The Hospital's
expertise includes ambulatory and hospital care, teaching, research,
and the evaluation of health technologies. The Hospital also provides
general and specialized acute care in accordance with its patients'
clinical needs and its subspecialized areas of expertise. In
addition, the Hospital's location allows it to offer medical and
surgical care to the boroughs of Sainte-Foy/Sillery. The Hospital
also has an in-house research center that is renowned worldwide and
supported by Fonds de recherche en sante du Quebec (Quebec Health
Research Council). The main goal of the Laval Hospital Research
Center is to slow the obesity epidemic and the progression of
cardiovascular and pulmonary disease through research and prevention.
The Laval Hospital Research Center has focused its development around
this vision and aims to become the leading North American research
center in cardiology, pneumology, and obesity. In order to achieve
this goal, the Center has undertaken a three-phase development plan,
two phases of which are currently underway. This expansion of
existing facilities will create some 200 jobs.
The Hopital Laval Research Center is one of the 38 affiliated
research centers of Universite Laval. Located in Quebec City,
Universite Laval was the first francophone university created in
North America. Its 17 faculties offer comprehensive undergraduate and
graduate programs to 38,000 students including 10,000 students.
Web Site :


Press Contacts : Jean-Pierre Despres, Ph. D., Hopital Laval, institut
universitaire de cardiologie et de pneumologie, Phone :
+1-(418)-656-4863, Fax : +1-(418)-656-4610, E-mail :