Rimonabant Helps With Weight Loss and Smoking Cessation

On March 9, at the American College of Cardiology Scientific Sessions in New Orleans, investigators presented details of their studies with rimonabant (trade name: Acomplia) - the first of a new class of drugs (selective CB1 blockers) aimed at helping with weight loss and smoking cessation. CB1 blockers act on the endocannabinoid system (the EC system), a natural system that modulates the body's energy balance and nicotine dependence. An over-stimulated EC system is thought to play a role in obesity and in tobacco dependence, and CB1 blockers are supposed to reduce this overstimulation. In a press release 3 weeks ago, the makers of rimonabant (Sanofi-Synthelabo,) indicated that the studies were favorable.

Data from two studies with rimonabant were reported this week. In the first, called the Stratus-US study, the drug's effect on smoking cessation was evaluated. In this study, 787 smokers (average of 23 cigarettes per day) were randomized to receive either placebo, or rimonabant in doses of either 5 mg or 20 mg per day. The patients received the study drugs for 10 weeks. They were permitted to continue smoking for the first 2 weeks, but were instructed to attempt to quit smoking on Day 15. The number of patients who had not smoked during the last 4 weeks of the 10 week period were tabulated. Of patients who took 20 mg of rimonabant, 36% had quit smoking. Of patients who took either placebo or 5 mg rimonabant, only 20% successfully quit. Further, of those patients who quit smoking, the ones taking either placebo or 5 mg rimonabant gained 84% more weight than those taking 20 mg rimonabant. Thus, rimonabant at 20 mg per day significantly increased the rate of successfully quitting smoking, and also greatly reduced post-smoking-cessation weight gain.

In the second study (the RIO-Lipids study,) 1036 patients who were either overweight or obese and who had blood lipid disorderswere also randomized to one of three groups (placebo vs. 5 mg/day or 20 mg/day rimonabant). After 1 year of treatment, patients receiving 20 mg rimonabant lost an average of about 20 pounds of weight, compared to 5 pounds for patients on placebo. Further, patients receiving 20 mg rimonabant had significant improvements (compared to placebo) in waist circumference, HDL levels, triglyceride levels, CRP levels, and insulin sensitivity. For patients with metabolic syndrome at baseline (which included about 50% of the study population), half of those taking 20 mg rimonabant no longer had metabolic syndromeat the end of the study.

The drug was said to be well tolerated. The only relatively common side effects were mild GI side effects and dizziness, and these were said to be transient.

There is still a lot we don't know about rimonabant, and further studies will be required before the drug is released - which probably won't happen for almost 2 years. Clearly, this is a drug that has "blockbuster" written all over it. If it turns out to be as effective and as safe as these early studies suggest, its uptake once released has the potential to be explosive - literally millions of patients may be receiving it within a short period of time. Given this fact, along with the fact that this drug is the first of a brand new class and thus there is no long-term experience with any similar substance, we can predict that the FDA will be cautious with its approval. The agency will be in a tough spot. They'll be getting a lot of pressure from both doctors and the general public to get this drug out there. But if there turns out to be some relatively uncommon (say, 1 per 5,000 patients) but devastating side effect, widespread early adoption of the drug may mean that hundreds or even thousands might experience that side effect before it is recognized.

So: real, pharmaceutical help for smoking cessation, weight loss, metabolic syndrome, and HDL levels may be on the horizon - but hold your horses. The drug will not be available to you for a couple of years - and even then, you might be wise to wait for a year or to two see if unexpected but nasty side effects eventually turn up. For at least the short-term future, we'll be left to resort to the old-fashioned methods for weight control and smoking cessation.

More about Zyban

The antidepressant drug Zyban is one of the newest – and reportedly one of the most effective – weapons in the anti-smoking arsenal.

What is Zyban?
‘Zyban’ is the drug’s trade name. The active ingredient is bupropion hydrochloride. Bupropion was originally designed as an antidepressant medication (marketed as Wellbutron), but which has been found to have an additional important function: it suppresses the urge to smoke in many people addicted to nicotine.


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How does Zyban work?
The way Zyban works is imperfectly understood, but it seems to affect the part of the brain associated with addiction, and increases levels of certain neurotransmitters (chemicals involved in transmitting messages between the nerve cells). Zyban is thought to increase the availability of two of these neurotransmitters, noradrenaline and dopamine, which moderate mood and control various other brain processes. The result is that Zyban simulates the effects of nicotine, and thus dampens the urge to smoke. Zyban also reduces the physical symptoms of nicotine withdrawal.

Zyban is considered to be as effective as nicotine replacement therapy (NRT) methods like the patch in helping smokers quit. Some studies show that approximately a third of smokers who take Zyban to help them quit aren’t smoking one year after treatment, which is higher than the success rate for NRT, and considerably higher for smokers attempting to quit ‘cold turkey’.

Stop smoking and lose weight?

OBESITY TREATMENT

Under development by Sanofi-Synthelabo, rimonabant (Acomplia) shows promise as both a weight-loss and smoking-cessation drug. Research indicates that rimonabant significantly reduces abdominal obesity, raises high-density lipoprotein ("good" cholesterol) levels, lowers triglyceride levels, and improves other markers of metabolic syndrome.

In one study, obese patients taking rimonabant lost an average of 20 pounds (9 kg) in a year. In a second study, the drug helped smokers nearly double their chances of kicking the habit in 10 weeks-and, as a bonus, overweight subjects also dropped about a pound each. The most common adverse reactions were nausea, dizziness, and upper respiratory tract infections.

Rimonabant is the first of a new class of drugs that block certain receptors on brain and fat cells belonging to the endocannabinoid (EC) system. Nicotine and the active ingredient in marijuana both attach to EC system receptors. Blocking these receptors seems to reduce both appetite and the urge to smoke.