It’s been several years in the making and believe-it-or-not it’s been 10-years since a new weight loss drug has been approved, but now there’s a new “kid on the block” and it’s expected to be big news as it represents something of a breakthrough in the management of obesity. The name of this new drug is Acomplia.
Acomplia contains a chemical called Rimonabant and it represents one of the latest and indeed most novel methods for controlling body mass because it operates by being a cannabinoid receptor antagonist. This means that it prevents the normal action of endogenous cannabinoid in the brain from stimulating the so-called CB1 receptors. It would appear that these receptors stimulate appetite and therefore when they are “subdued” so is the need to eat.
The origin of this idea was the realization that smoking cannabis tends to induce the sensation to eat, the so-called munchies. This lead scientists to believe that the inhibition of the cannabinoid receptors may lead to the opposite effect. There must have been some interesting proposals as to how to conduct the clinical trials!
So it was the pharmaceutical giant Sanofi-Aventis that set out in 2001 to begin clinical trials to establish whether this approach could benefit obese individuals. The results of those trials have resulted in much excitement and the anticipation of the drug’s release, under the brand name of Acomplia. According to Jean-Francois Dehecq, Sanofi’s CEO, Acomplia could peak annual sales of $3.6 billion an amount unheard of, even in the lucrative market of weight loss treatments.
So what’s all the fuss about? Let’s look at some of the clinical trials.
Findings of a human 2-year trial with Acomplia were presented at the American Heart Association conference in New Orleans in November 2004. It indicated that 33% of people using Acomplia managed to lose 10% of their body weight and kept their weight down throughout the study period of 2-years, a further third lost 5% of their body weight and kept that weight off too.
Additional long term human study results were presented in March 2005 at the American College of Cardiology. 1036 patients who were either overweight or obese and who also had blood lipid disorders were randomized to one of three groups, those being placebo, 5 mg./ day or 20 mg./ day of Acomplia. After 1-year of treatment, patients receiving 20 mg./ day Acomplia had significant improvements (compared to placebo) in waist circumference, as well as HDL (good cholesterol) levels, triglyceride levels, CRP levels and insulin sensitivity.
During the trial the drug was well tolerated. The only relatively common side effects were mild gastrointestinal effects, dizziness and these were noted to be transient.
“Those who stay on the drug for a year show remarkable weight loss: on average 17 pounds (7.7 Kg).” said Jean Pierre Despres, PhD., Professor of food and nutrition sciences at Lavel University in Montreal. “Plus we saw a real reduction in waist circumference of 3 inches (8 cm).”
But aside from the weight loss, the numerous trials conducted to date have also highlighted other possible advantages for Acomplia.
In June 2005 the American Diabetes Association at their congress in San Diego reported the results of a 1-year study on 1045 people with type-II diabetes.
They found that 20 mg./ day of Acomplia improved HbA1C (a measure of blood sugar control), dyslipidemia (abnormal levels of fat in the blood) and systolic blood pressure. “The [trial] results indicated that Acomplia delivered a clinically meaningful reduction in HbA1c and may offer a broad range of cardiometabolic risk factor improvements that are essential for the comprehensive management of people with type II diabetes,” said Professor Scheen, who went on to say that; “even in a patient population with an average HbA1c levels at a point where further control is difficult to achieve, rimonabant was still able to achieve a clinically significant reduction in HbA1c.”
The study followed 1045 people in 11 different countries, all of whom had type-II diabetes. 43% of patients on 20 mg./ day of Acomplia achieved HbA1c levels below 6.5% (the level recommended by the American Association of Clinical Endocrinologists), that was more than double to those on placebo.
Even the diabetic patients had significant weight loss with Acomplia, an average of 11.7 lbs (5.3 Kg) versus 3 lbs (1.4 Kg) for those on placebo, and most significantly a waist circumference reduction of 2 inches (5.3 cm) for those using Acomplia compared to 0.7 inches (1.9 cm) for those using placebo.
“The weight loss reported for Acomplia in patients with diabetes may be an important finding,” commented Dr. Michael Jensen, Professor of Medicine at the Mayo Clinic. He added that; “Glycemic control with current therapies is often associated with weight gain. This weight gain can diminish the benefits of treatment and lessen the overall improvement in cardiometabolic risk.”
In the same diabetes study (as above), HDL cholesterol (the so-called good version) and triglycerides were improved in patients taking Acomplia at 20 mg./ day. Specifically HDL cholesterol increased on average by 15.4% in the Acomplia group (compared to 7.1% in the placebo group) and triglycerides were reduced by 9.1% on average in the Acomplia group compared to an increase of 7.3% in the placebo group.
Side effects noted in these studies were mainly mild and transient consisting (in order of frequency) of nausea, dizziness, diarrhoea, vomiting, hypoglycaemia, fatigue and anxiety.
Clinical trials; Smoking
It would appear that the same CB1 receptors whilst having a role in controlling diet and factors associated with diabetes and cardiovascular issues may also be a prominent factor in helping to quit smoking.
It is quite obvious that smoking is detrimental to health, but as Robert Anthenelli, M.D., Professor of psychiatry at the University of Cincinnati stated; “smoking cessation is an enormous struggle for many people. People who smoke are at a high risk for cardiovascular disease. It is imperative to do anything and everything we can to treat tobacco dependence. Acomplia represents a potentially promising new treatment option that can help people stop smoking while curbing post cessation weight gain. This may be a major step forward in smoking cessation.”
To test this, a double-blind, placebo controlled study enrolled 787 smokers. Their average age was 42 and they smoked 23 cigarettes a day, after having been smokers for 11 to 24 years. These figures classified them as moderate to heavy smokers. 16
Over a period of 10-weeks they received either 5 mg., 20 mg. of Acomplia or a placebo. Abstinence was measured within the first 4-weeks of the trial by measuring carbon monoxide concentrations in their expired air (therefore reducing the chances of patients lying about their habit).
The results were that 20 mg./ day of Acomplia doubled the chance of quitting when compared to placebo, with 36.2% of those using Acomplia quitting compared to 20.6% on placebo.
Interestingly, during the post-cessation period, the time when typically smokers gain weight (normally because they substitute their habit for eating), and the Acomplia patients showed an actual loss of weight of an average of 0.5 lb (0.3 Kg) whereas the placebo group gained on average 2.5 lbs (1.1 Kg).
Is it any wonder that Sanofi are expecting Acomplia to be a blockbuster drug? Consider that it has shown itself to be effective in reducing individual’s weight- on average by 10%, furthermore reducing the usually “hard to effect” waist lines and even maintaining that weight loss for at least 2-years, thus aiding those billion people worldwide now classified as obese.
In addition, it also appears to benefit type-II diabetes, a pandemic currently estimated to affect nearly 200 million people worldwide and rising fast.
On top of that it positively aids the correction of cholesterol and triglyceride ratios with its relevance for improved cardiovascular health.
Plus, if you’re a smoker, Acomplia could be the drug of choice to also help you kick that unhealthy habit.
The undoubted forthcoming success of Acomplia is highly likely to spark an entirely new generation of drugs.
- Acomplia (Rimonabant), investigational agent for the management of obesity. www.drugdevelopment-technology.com
- New study confirms benefits of Rimonabant in weight loss. www.news-medical.com
- Rimonabant study shows significant improvements in HbA1c and cardiometabolic risk factors in people with type II diabetes. Medical Study News, Sunday June 2005.
- Amy Tsao. Has obesity met its match? Business week online, April 8, 2004.
- Abstracts from the 2004 Scientific Sessions of the American Heart Association. November 7-10, 2004, New Orleans, Louisiana, USA. Circulation. 2004 Oct 26;110(17 Suppl):III1-835
- Highlights from the American College of Cardiology Annual Scientific Session 2005: March 5-9, 2005, Orlando, Florida] Rev Med Suisse. 2005 May 4;1(18):1234, 1236-7
- A 2 in 1 drug helps to lose weight and quit smoking, Yahoo ANI news, February 22, 2005.
- American Diabetes Association website www.diabetes.org
- Data shows new drug, rimonabant, helps smokers quit while limiting post cessation weight gain, www. eurekalert.org, 9 March, 2004.