Posted by Larry Hoover on August 31, 2004, at 22:32:24
In reply to endocannabinoid know as arachidonoyl ethanol amide, posted by lil' jimi on August 20, 2004, at 20:43:45
http://www.cnw.ca/fr/releases/archive/August2004/29/c4670.html
New Study Confirms Benefits of Rimonabant in Weight Loss, Waist Circumference Reduction and Metabolic Risk Factor Improvement
1st year results of RIO-Europe study presented at the European
Society of Cardiology (ESC) 2004 congressANTWERP, Belgium, Aug. 29 /CNW/ - First year results of the two year
trial Rimonabant In Obesity - Europe (RIO-Europe), a Phase III clinical study
comparing placebo to rimonabant, the first agent in a new therapeutic class
known as selective cannabinoid type 1 (CB1) blockers, showed that overweight
or obese people taking rimonabant 20mg once daily benefited from a significant
reduction in their body weight, waist circumference - a marker of the
dangerous abdominal obesity - and improvements in their lipid and glycemic
profiles. The improvement in lipids (HDL-cholesterol and triglycerides) was
demonstrated to be partially independent from weight loss, implying a direct
effect of the drug on these important metabolic cardiovascular risk
parameters. The trial findings also revealed a significant decrease in the
percentage of patients with metabolic syndrome(1) in the rimonabant 20 mg/day
group compared to placebo. These new results from the RIO-Europe study confirm
rimonabant's potential to become an important tool in the reduction of
cardiovascular risk factors by lowering body weight, improving metabolic
syndrome-associated parameters in overweight/obese subjects and aiding in
smoking cessation as presented earlier this year.1) Metabolic Syndrome is a term that encompasses a series of health risks
or conditions that increase a person's chance to develop heart disease, stroke
and diabetes. According to the ATP III definition, metabolic syndrome includes
at least 3 of the following criteria: abdominal obesity: waist circumference
Men greater than 102 cm (40 inches), Women greater than 88 cm (35 inches);
hypertension: greater than or equal to 130/85mmHg; hypertriglyceridemia:
greater than or equal to 150mg/ dL; Low HDL cholesterol: Men less than
40mg/ dL, Women less than 50mg/ dL; Abnormal fasting glucose: greater than or
equal to 110mg/ dL. 1RIO Europe, an international, multicentre, randomized, double-blind,
placebo-controlled, parallel-group study compared rimonabant 20mg/day
and 5mg/day to placebo in 1,507 overweight/obese patients (Body Mass
Index (BMI) greater than or equal to 30 kg/m(squared) or BMI greater than 27
with co-morbidity (e.g. dyslipidemia, hypertension) in 60 centres across
Europe (Belgium, Finland, France, Germany, the Netherlands, Sweden) and the
United States for a period of 2 years. The announcement made at the ESC 2004
concerns the first year data of the study. Patients treated for one year with
rimonabant 20mg/day lost an average of 8.6kg (about 19 lbs) (p less than 0.001
vs placebo) compared to 4.8kg (about 11 lbs) for patients on rimonabant
5mg/day (p equals 0.038 vs placebo) and 3.6kg (about 8 lbs) for those on
placebo. Nearly 70% of patients treated with rimonabant 20mg/day lost more
than 5% of their initial body weight (p less than 0.001 vs placebo), compared
to 44.2% of patients in the rimonabant 5mg/day group (p equals 0.002 vs
placebo) and 30.5% in the placebo group. Moreover, 39% (p less than 0.001 vs
placebo) of patients on rimonabant 20mg/day lost more than 10% of their
initial body weight compared to 15.3% of those on rimonabant 5mg/day and 12.4%
of those on placebo. Patients on rimonabant 20mg/day also had an average
decrease in their waist circumference of 8.5 cm (about 3.5 inches) (p less
than 0.001) versus 5.3 cm (2 inches) for those on rimonabant 5mg (p equals
0.002 vs placebo) and 4.5 cm (about 1.5 inches) for those on placebo. The
number of patients diagnosed as having metabolic syndrome at baseline (42.2%)
was reduced by more than half (19.6%) after treatment with rimonabant 20mg
(p less than 0.001 compared to placebo). In addition to weight loss, a
statistically significant improvement in metabolic risk factors with
rimonabant 20mg vs. placebo was also observed. In patients treated for one
year with rimonabant 20 mg/day, HDL-cholesterol (good cholesterol) increased
by 27.0% (p less than 0.001 vs placebo), compared to 19% in the rimonabant
5mg/day group and 17.3% in the placebo group. Weight loss accounted for only
approximately half the improvement in HDL seen with rimonabant 20mg vs.
placebo, implying a significant direct effect of the drug on lipid metabolism,
independent of weight loss (p equals 0.005).
In patients treated for one year with rimonabant 20mg, triglycerides
were reduced by 10.6% in patients on rimonabant 20 mg (p less than 0.001
vs. placebo), while increasing by 4.9% for rimonabant 5mg and by 6.6% for
placebo. As seen with HDL, weight loss accounted for only approximately
half the improvement in triglycerides seen with rimonabant 20mg vs. placebo,
implying a significant direct effect of the drug on lipid metabolism,
independent of weight loss (p equals 0.005). An improved insulin response as
demonstrated by an Oral Glucose Tolerance Test was also observed. During the
2 hour test, patients on rimonabant 20 mg had to produce less insulin to
metabolize their glucose compared to those on placebo (reduction by 11.0 micro
IU/ml vs baseline compared to 2.3 micro IU/ml in the placebo group; p equals
0.019 ). "The findings of the RIO-Europe trial are totally consistent with
those of the RIO-Lipids trial announced earlier this year at the American
College of Cardiology meeting. Patients on rimonabant 20mg/day experienced
significant benefits in terms of weight loss, reduction in waist circumference
and also experienced sizeable improvements in their lipid and glycemic
profiles. What is even more interesting is the effect rimonabant 20mg has on
metabolic cardiovascular risk factors, which is independent of weight loss,"
said Luc Van Gaal, M.D., Professor of Diabetology, Metabolism and Clinical
Nutrition, University Hospital Antwerp, Belgium, Principal Investigator of the
RIO-Europe trial. "We are looking forward to the full 2 year findings of the
RIO-Europe trial to see if these impressive results are maintained," he added.
The RIO-Europe findings also confirmed the good safety profile of rimonabant.
Side effects were mainly mild and transient and most frequently involved
nausea (4.3 %, 5.1% and 12.9 % for placebo, rimonabant 5mg and rimonabant 20mg
respectively), diarrhoea (3.0%, 6.0 % and 7.2% for placebo, rimonabant 5mg and
rimonabant 20mg respectively) and dizziness (4.9 %, 7.0 %, 8.7 % for placebo,
rimonabant 5mg and rimonabant 20mg respectively). Only in a very small number
of cases did these side effects lead to discontinuation of drug use.
Overall dropout rates in the three groups were similar (41.6% in the
placebo group vs. 37.3% for rimonabant 5mg and 39.4%, for rimonabant 20mg).
No difference was observed in the three groups with regards to scores measured
by the Hospital anxiety depression scale. Importantly, rimonabant was also
shown to have a good cardiovascular safety profile. The RIO-Europe trial is
one of four Phase III studies comprising the RIO programme, which assesses the
efficacy and safety of rimonabant in weight reduction and metabolic risk
factor improvement in over 6,600 overweight and obese patients world-wide.
Rimonabant is also under investigation as an aid to smoking cessation in the
STRATUS programme. The results of the STRATUS US trial presented earlier this
year demonstrated that rimonabant 20mg doubled the odds of quitting smoking
vs. placebo (p equals 0.002) without weight gain (on average patients lost
0.3kg (0.7 lb) on rimonabant 20mg vs. a 1.1kg (2.4 lb) weight gain for
patients on placebo (p less than 0.001). Preclinical studies have demonstrated
the role of the endocannabinoid system (ECS), via the CB1 receptor, in the
central and peripheral regulation of energy balance, as well as in the control
of nicotine dependence. Rimonabant is the first selective cannabinoid type 1
(CB1) blocker to be developed for the management of cardiovascular risk
factors including obesity, metabolic syndrome, dyslipidemia, type 2 diabetes
and tobacco dependence. Metabolic parameter improvements observed with
rimonabant are beyond those expected through weight reduction. The new
clinical results from the RIO-Europe study confirm that by reducing body
weight and improving metabolic parameters in overweight/obese subjects,
rimonabant may become an important tool in the cardiovascular risk factor
reduction armamentarium.
poster:Larry Hoover
thread:377884
URL: http://www.dr-bob.org/babble/20040830/msgs/385068.html