Related Results

Lancet, BMJ studies sound concern over anti-obesity drug rimonabantRimonabant improves cardiovascular risk profileRimonabant improves cardiovascular risk profileNew drug application for rimonabant pulledRimonabant enhanced weight loss success, improved lipids

“I have never before seen a 27% increase in HDL [cholesterol] with any drug–not statins, not even fibrates,” observed Dr. Van Gaal, professor of internal medicine and diabetology at the University of Antwerp (Belgium).
At baseline, 42% of patients in the rimonabant 20-mg arm met criteria for metabolic syndrome, placing them at increased risk for cardiovascular disease. After 1 year of therapy in what will be a 2-year trial, the prevalence of metabolic syndrome was slashed by 53%.
RIO-Europe is a seven-nation study involving patients with a mean body mass index of 36 kg/[m.sup.2] and an average waist circumference of 110 cm. As is typical of obesity clinical trials, 80% were women.
Participants were encouraged by dietitians and counselors to modify their lifestyle by increasing physical activity and adopting a diet with a 600-cal/day deficit. One-fifth of subjects were randomized to placebo, while the remainder received either 5 mg or 20 mg of rimonabant daily.
The placebo response was high, which Dr. Van Gaal attributed to the counselors’ dedication. Thirty-one percent of patients who completed 1 year of placebo therapy lost more than 5% of their initial body weight, and although that’s an impressive figure, it is well below those of the rimonabant groups: 44% in the patients receiving 5 mg/day and a 67% rate in those receiving 20 mg/day.
Of patients on 20 mg/day rimonabant, 39% lost more than 10% of their initial body weight, as did 15% of those on 5 mg/day and 12% of those on placebo. It’s known that a 10% loss in body weight coupled with an 8- to 10-cm decrease in waist circumference translates into a 25%-30% reduction in metabolically harmful visceral fat. A significantly improved insulin response on an oral glucose tolerance test was also noted in patients on 20 mg/day rimonabant.
Earlier studies showed that weight loss on rimonabant is primarily due to decreased cravings for two food groups: sweets and fats, Dr. Van Gaal said.
The only side effects more common in rimonabant patients than placebo patients were mild transient nausea and diarrhea. Concern about possible psychiatric side effects raised in an earlier smaller study proved groundless.
About 40% of patients in each of the three study arms dropped out, primarily as a result of unmet expectations. Participants were counseled that a 5%-10% weight loss was both realistic and medically meaningful, but many still sought a 20%-25% weight loss. “They always hope for a miracle,” Dr. Van Gaal observed.
RIO-Europe was sponsored by Sanofi-Aventis. The company is aggressively pursuing development of rimonabant in eight phase III clinical trials comprising more than 13,000 patients. The focus is on two separate indications: weight loss and smoking cessation. Previously presented smoking cessation studies showed that rimonabant doubled the quit-success rate, compared with placebo, while enabling patients to avoid the associated weight gain that often thwarts smoking cessation attempts.
Dr. Van Gaal said the remaining phase III rimonabant trials are slated for completion by year’s end, including the 2,500-patient RIO-North America trial to be presented in November at the annual scientific sessions of the American Heart Association. He added that during the first half of next year Sanofi-Aventis plans to file for Food and Drug Administration marketing approval for the two indications.
Discussant Dr. Philippe Gabriel Steg of Bichat Hospital in Paris commented that in his view the most important finding in RIO-Europe was that weight loss accounted for only about half the improvement in HDL-cholesterol and triglyceride levels. This implies the drug has direct metabolic effects beyond weight loss.
The endocannabinoid system is a recently discovered system involved in regulation of energy balance. “The system is often silent but can become overactive if stimulated by excess food intake or nicotine abuse,” Dr. Van Gaal explained.
Rimonabant blocks the endocannabinoid type 1 receptor both centrally and peripherally. The central effect leads to decreased food intake and can help control nicotine dependence. Peripherally, the drug acts on adipocytes to increase levels of adiponectin, which reduces insulin resistance and increases HDL cholesterol.

Related Results

Lancet, BMJ studies sound concern over anti-obesity drug rimonabantRimonabant improves cardiovascular risk profileRimonabant improves cardiovascular risk profileNew drug application for rimonabant pulledRimonabant enhanced weight loss success, improved lipids

The latest of these trials, the Rimonabant in Obesity (RIO)–Diabetes study, suggests similar benefit among overweight and obese patients with type 2 diabetes.
“Patients with type 2 diabetes often have multiple cardiovascular risk factors. Current [glucose-lowering] therapies are often associated with weight gain, which can have a deleterious effect on overall cardiometabolic risk. Therefore, a new approach is needed.” said RIO-Diabetes principal investigator Dr. Scheen, head of the Division of Diabetes, Nutrition, and Metabolic Disorders at the University of Liege, Belgium.
The 1-year, randomized, double-blind, controlled trial enrolled a total of 1,045 overweight or obese patients (body mass indexes [kg/[m.sup.2]] of 27-40) with type 2 diabetes who were aged 18-70 years, and who had already been taking either metformin or a sulfonylurea for at least 6 months.
They were randomized to receive either 5 mg or 20 mg/day of rimonabant or placebo, and all were advised to reduce their daily caloric intake by 600 kilocalories. Two-thirds of the patients completed the 1-year trial.
The three groups were similar at baseline, with a mean age of 56 years, hemoglobin [A.sub.1c] of 7.5%, BMI of 34, and waist circumference of 110 cm. About 60% had hypertension, 55% had dyslipidemia, and 80% met criteria for metabolic syndrome. About two-thirds were taking metformin; one-third were taking sulfonylureas. They continued taking those medications throughout the study.
In the intent-to-treat analysis of the original 1,045 patients with the last observation carried forward, those randomized to 20 mg/day of rimonabant lost a mean of 5.3 kg, compared with 1.4 kg in the placebo group, a highly significant difference. Among the completers, the difference was 6.0 kg vs. 1.9 kg.
Similarly, waist circumference in the 20-mg rimonabant group was reduced by 5.2 cm, compared with 1.9 cm in the placebo group in the initial cohort; the reductions were 6.0 cm vs. 2.4 cm among the completers. More modest results were seen with 5-mg rimonabant, Dr. Scheen noted.
A total of 55.9% of the completers in the 20-mg group lost 5% or more of their initial body weight, compared with 19.5% of the placebo group (49.4% vs. 14.5% in the intent-to-treat analysis), whereas 21.4% and 3.0% of the completers, respectively, and 16.4% and 2.0% of the entire initial group lost 10% or more of their initial body weight. These results are similar to those seen among the nondiabetics in the other RIO trials, “which is remarkable, taking into account the well-known difficulty of diabetics to lose weight,” he said.
Hemoglobin [A.sub.1c], already relatively good at baseline, was improved further with rimonabant at 1 year in the intent-to-treat analysis.
In the 20-mg arm, mean Hb[A.sub.1c] dropped from 7.3% to 6.7%, while remaining unchanged–7.2% to 7.3%–in the placebo group. Here, the difference from placebo was significant for both the 5-mg arm (a 0.2 percentage point drop) and the 20-mg group (a 0.7 percentage point drop). The drop in Hb[A.sub.1c] was identical for those taking metformin and sulfonylureas, he added.
The proportion of patients achieving Hb[A.sub.1c] values of 6.5% or lower (the American Association of Clinical Endocrinologists’ target) was 42.9% with 20-mg rimonabant and 20.8% with placebo, which was a doubling of the success rate. A statistical analysis using a covariance method determined that the weight loss accounted for just 0.3 of the 0.7 percentage point drop in Hb[A.sub.1c] among the patients in the 20-mg arm. It could not explain the other 0.4, suggesting an intrinsic weight-independent metabolic effect of rimonabant.
Lipid improvements also occurred with rimonabant in the intent-to-treat analysis, similar to what was seen among nondiabetics in the other RIO trials.
Levels of HDL cholesterol increased by 15.4% from baseline with 20-mg rimonabant, compared with 9.2% with 5 mg and 7.1% with placebo. As in the other trials, more than half of the increase in HDL cholesterol could not be attributed to weight loss.
All four RIO trials–RIO-Europe, RIO-North America, RIO-Lipids, and now RIO-Diabetes–have shown similarly consistent improvements in components of the metabolic syndrome, Dr. Scheen pointed out.
Safety and tolerability of rimonabant in RIO-Diabetes were also similar to those seen in the previous trials.

Related Results

Lancet, BMJ studies sound concern over anti-obesity drug rimonabantRimonabant improves cardiovascular risk profileRimonabant improves cardiovascular risk profileNew drug application for rimonabant pulledRimonabant enhanced weight loss success, improved lipids

In the double-blind, placebo-controlled Study Evaluating Rimonabant Efficacy in Drug-Naive Diabetic Patients (SERENADE), 138 patients receiving rimonabant 20 mg/day were compared with 140 patients on placebo. All patients were at least 18 years old, had a history of type 2 diabetes diagnosed 2 months to 3 years prior to the study, and had no previous insulin therapy, other than insulin for gestational diabetes or for short-term hospitalization. None had taken oral antidiabetic drugs beyond 4 months, and such drugs were discontinued at least 6 months prior to the study. All had a stable weight, and Hb[A.sub.1c] levels of at least 7% but no greater than 10%.
The patients were treated at any of 56 centers in the United States, Argentina, Chile, Germany, Hungary, the Netherlands, and Poland. The study’s primary end point was reduction in Hb[A.sub.1c] level.
At baseline, both study arms had a mean Hb[A.sub.1c] of 7.9%; at 6 months, this measure had dropped to a mean of 7.1% in the rimonabant group, compared with 7.5% in the placebo group, Dr. Julio Rosenstock said at a press briefing during the congress.
In a subgroup of patients with baseline Hb[A.sub.1c] levels of at least 8.5%, the difference between the groups was even more pronounced, with the rimonabant group’s mean level dropping to 7.0% at 6 months, compared with 8.3% for the placebo group.
Overall, the portion of the treatment population achieving an Hb[A.sub.1c] level of less than 7% was 51% in the rimonabant group and 35% in the placebo group.
Rimonabant also helped patients achieve significant reductions in body weight and waist circumference, said Dr. Rosenstock, clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas. Patients taking the study drug saw a mean 6.7-kg reduction, compared with a mean 2.8-kg reduction for those taking placebo. Waist size was reduced by a mean of 6 cm for those on rimonabant, vs. 2 cm for those on placebo. (All data were based on intent to treat, with the last observation carried forward.)
The effect on Hb[A.sub.1c] appears to be independent of weight loss, Dr. Rosenstock said, noting that according to analysis of variance, 57% of the drop in Hb[A.sub.1c] was a direct effect of rimonabant.
Rimonabant also was associated with significantly greater improvements in cardiometabolic measures, compared with placebo. Serum levels of adiponectin rose by a mean of 1.6 mcg/mL in the treatment group, compared with a 0.2-mcg/mL decrease in placebo patients. Insulin resistance levels (known as HOMA-IR levels) rose by a mean of 0.33 units in the placebo group and dropped by a mean of 1.89 units in the rimonabant arm. The mean HDL cholesterol level was increased by 10% on rimonabant vs. by 3% on placebo, while mean triglyceride levels fell by 16% on the drug, vs. 4% on placebo.
The most common side effects associated with rimonabant were dizziness (11%), nausea (9%), upper respiratory tract infection (7%), anxiety (6%), and depressed mood (6%). In the treatment group, there were 13 discontinuations (9%), vs. 3 (2%) in the control group.
Sanofi-Aventis, which markets rimonabant (Acomplia) in Europe as a weight-loss drug, sponsored the study. In February 2006, the U.S. Food and Drug Administration issued an “approvable letter” for that indication–but not for use as a diabetes drug. The company submitted its response in October.
BY JOHN R. BELL
Associate Editor
COPYRIGHT 2007 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning

Related Results

Lancet, BMJ studies sound concern over anti-obesity drug rimonabantRimonabant improves cardiovascular risk profileRimonabant improves cardiovascular risk profileNew drug application for rimonabant pulledRimonabant enhanced weight loss success, improved lipids

COPYRIGHT 2007 Racher Press, Inc.
COPYRIGHT 2008 Gale, Cengage Learning

Related Results

Lancet, BMJ studies sound concern over anti-obesity drug rimonabantRimonabant improves cardiovascular risk profileRimonabant improves cardiovascular risk profileNew drug application for rimonabant pulledRimonabant weight loss sustained at 2 years

Rimonabant is under consideration at the Food and Drug Administration for two indications, weight management and smoking cessation. Sanofi Aventis, which would market the drug as Acomplia, announced last month that the company had received letters from the FDA saying that the weight management indication is “approvable,” but the smoking cessation indication is “nonapprovable.”
The RIO-NA study examined weight loss: Dr. Pi-Sunyer and associates assessed 3,045 obese or overweight individuals over 2 years at 64 U.S. and 8 Canadian clinical research centers.
All participants were instructed to follow a low-calorie diet and to increase their physical activity throughout the study.
They also were randomly assigned to take either 5 mg/day of rimonabant (1,216 subjects), 20 mg/day of rimonabant (1,222 subjects), or a placebo (607 subjects).
Only 51% of subjects in the low-dose rimonabant group, 55% in the high-dose rimonabant group, and 51% in the placebo group completed the first year of the study, the investigators said (JAMA 2006;295:761-75).
At that point, those participants who were taking either dosage of rimonabant showed a greater mean weight reduction and a greater mean decrease in waist circumference than participants taking placebo. The drug also decreased the prevalence of the metabolic syndrome.
The proportion of subjects who achieved a weight loss of 5% or more was 49% on high-dose rimonabant, 26% on low-dose rimonabant, and 20% on placebo.
Individuals who continued taking rimonabant for the second year of the study maintained a mean weight loss of 7.4 kg, while those who switched to placebo for the second year regained most of the weight they had lost. The same pattern held true for waist size.
After 2 years, 40% of the subjects taking high-dose rimonabant achieved a weight loss of 5% or greater, compared with 19% of those taking the placebo.
Compared with subjects who received placebo, those who took 20 mg of rimonabant showed favorable changes in levels of HDL cholesterol, triglycerides, fasting insulin, and insulin resistance, the researchers said.
These improvements “appeared to be approximately twice that expected from the achieved weight loss alone, suggesting a direct pharmacological effect of rimonabant on glucose and lipid metabolism beyond the weight loss achieved,” they reported.
In addition to the high dropout rate, the limited racial diversity of the study cohort, which predominantly involved white women, may diminish the generalizability of the study findings, the investigators added.
In an editorial comment, Dr. Denise G. Simons-Morton and associates at the National Heart, Lung, and Blood Institute, Bethesda, Md., said that the study had many strengths but “an overriding concern is the failure to obtain final weight measurements on about half of the randomized participants.”
“Randomization no longer serves its purpose when investigators fail to analyze those who do not adhere,” they said (JAMA 2006;295:826-8).
It would have been far more convincing to have analyzed actual data on the vast majority of those randomized,” Dr. Simons-Morton and her associates said.
In addition, the drug’s possible adverse effects must be studied in more detail. Dr. Pi-Sunyer and associates said rimonabant was “generally well tolerated, with adverse effects that were mostly mild and moderate.”
BY MARY ANN MOON
Contributing Writer
COPYRIGHT 2006 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning

Related Results

Lancet, BMJ studies sound concern over anti-obesity drug rimonabantRimonabant improves cardiovascular risk profileRimonabant improves cardiovascular risk profileNew drug application for rimonabant pulledRimonabant enhanced weight loss success, improved lipids

In this latest study, the researchers found that mice fed a low-fat diet and ethanol showed an increase in the gene encoding the CB1 cannabinoid receptor and in liver levels of an endocannabinoid called 2-arachidonoylglycerol (2-AG). These mice developed fatty …

Read the full article with a Free Trial at MyWire.

Related Results

Cheyenne, Wyo.-area doctors skeptical of ’super bill’ for weight loss, smoking.

Pounds-off prescription

Blockbuster obesity drug aims to win $4bn sales for Sanofi-Aventis

Obesity drug ‘to make a splash’.(Sanofi-Aventis)

Long-Term Benefits of Rimonabant Confirmed in Two-Year Study.

RIO (Rimonabant In Obesity)-North America was a Phase III, multicenter, randomized, double-blind, placebo-controlled trial which compared two fixed-dose regimens of Acomplia (5mg and 20mg once-daily) to placebo for a period of two years. The study involved …
Want to read the whole article? You can purchase it here. It’s quick and easy.

Before opening fire against enemy collect as much as possible information about him. For this particular moment obesity is your enemy, you are required to know few details about it. There are many categories of obesity but there can be only two root causes for all of them.

Genetical Disorder

Imbalanced and excessive diet with inappropriate physical work

Curing genetical disorder is not possible with all presently available techniques. Deformation caused by imbalanced and excessive diet can be cured by balancing your diet. An obese generally has a great affinity towards food so curbing his appetite is not simple. Moreover, it will be very cruel to starve yourself when you have access to delicious food. Killing hunger can be dangerous because whenever you feel hunger your liver and pancreas secretes bile and gastric juices. These acidic digestive juices can deteriorate tissues of your stomach when there is no food present in your stomach.

Can’t suppress appetite! Then, how can an obese fight with this disease? Diet pills are an answer to this question. There are many diet pills in the market like Xenical (Orlistat), Acomplia (Rimonabant) , Phentermine, Adipex. All these are appetite suppressants but work in a different manner. Rimonabant is the basic salt of diet pill Acomplia. Rimonabant blocks the working of CB-1 receptor, which send hunger signal to the brain. Only after getting these signals brain secretes hormone which stimulate secretion of bile juices. No signal means no urge for food and no secretion of bile juices and no harm to the delicate tissues of your stomach.

Regular smoker have highly active CB-1 receptors. Blockage of CB-1 receptor can also be helpful in curbing addiction for smoking. Henceforth, doses of 20mg of Rimonabant can do dual magic as suppressant of appetite and smoking.

Acomplia is available in the European market since June 2006. Consumption of Rimonabant is related with some initial benign side effects like dizziness, muscle cramp, gastro-intestine disorder, and constipation. These problems disappear within days because body generally adapts to the drug after use for few days. Doctor’s prescription for consuming this oral medicine is essential.

Get a new look with the help of Rimonabant and surprise people around you.

> PARIS, France, April 28 /PRNewswire/ — Sanofi-aventis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has adopted a positive opinion recommending to grant marketing authorisation in the European Union for ACOMPLIA(R) (rimonabant 20mg) for the following indication: ” As an adjunct to diet and exercise for the treatment of obese patients (BMI greater than or equal to 30kg/m2), or overweight patients (BMI > 27 kg/m2) with associated risk factors, such as type 2 diabetes or dyslipidemia (see section …

Read the rest of this article with a Free Trial at HighBeam Research.

Most Popular
When T Make Job Transfers: Good Reasons For Quitting Your Job
Awaken Your Audience: How To Seize Attention In Public Speaking
Time Management Tip: You Have To Track The Hand-offs
Strategic Management Tasks For The Small Business Owner
Market-based government through innovation: How public sector leaders are improving collaboration and focusing on citizens

The results of a two-year Phase III study in 3040 patients with rimonabant (Acomplia(TM)), the first in a new class of therapeutic agents called selective CB1 Blockers, demonstrate that the benefits achieved with rimonabant 20mg at the end of the first year of the study were sustained in the second year of therapy with a good safety and tolerability profile vs. placebo. The two year results of …

Read the rest of this article with a Free Trial at HighBeam Research.