Rimonabant Still Impressive, But. . .
Updated June 08, 2015.
By DrRich
At the recent American Heart Association Scientific Sessions 2004, new data were reported on the effectiveness of rimonabant for treating obesity. Rimonabant, an investigational drug from Sanofi-Aventis, is aimed at helping patients lose weight and quit smoking. Early trials with rimonabant have been promising. ( Read about these earlier weight loss and smoking cessation trials here.)
In this most recent trial, the RIO-North America trial, 3040 patients were randomized to receive either placebo or one of two doses of rimonabant (5 mg or 20 mg per day.).
Patients taking 20 mg rimonabant had significant weigh loss, decrease in waist circumference, improved insulin sensitivity, and increases in HDL cholesterol, compared to patients on placebo. (Those taking 5 mg also had more weight loss than placebo patients, but the magnitude of weight loss was much less.) These results were strikingly similar to those previously reported in the RIO-EUROPE trial.
In this trial, however, patients who took 20 mg rimonabant for 1 year were then re-randomized to either continue on rimonabant, or to switch to placebo. Patients who stayed on rimonabant for the second year maintained the same degree of weight loss (they did not lose additional weight,) while those switched to placebo gained weight. At the end of 2 years, patients who took rimonabant for one year and placebo for the second year had about the same amount of overall weight loss as patients who took placebo from the beginning.
Side effects included depression, anxiety and nausea. About 1 in 8 patients taking rimonabant dropped out of the study due to side effects.
Is there a dark side to rimonabant?
From the data that continues to accumulate, it appears that "so far so good" is the watchword with rimonabant. However, several observers at the AHA meeting urged caution. There are two very good reasons not to get too excited about this drug just yet. First, rimonabant is the first of a new class of drugs targeting the endocannabiniod system, which helps to regulate pleasure, relaxation, and pain tolerance. We still do not have a good notion of what happens when we interfere with this system on a very long-term basis (and from this new study, it seems obvious that treatment with rimonabant will have to be chronic.) The fact that significant depression was seen in at least some of the patients enrolled in the trials so far ought to raise a fair amount of caution. Further, neurologists point out that the endocannabinoid system helps to protect the brain under some circumstances (such as stroke and head injury,) and some worry that brain damage in these circumstances might be worse in patients taking drugs that block the endocannabiniod system. Even more scary, a recent article in the journal Multiple Sclerosis describes a patient whose previously subclinical case of multiple sclerosis became active when this drug was started.
The second reason not to get overly excited yet is that, while rimonabant has now been used in a few thousand patients, once it is market released its usage will explode to the hundreds of thousands or even millions of patients. (Judging from the volume of e-mails DrRich gets each time he writes about this drug, the pent-up demand is massive.) Once this happens, any disturbing side effects that now seem infrequent (or that haven't even been identified yet) may suddenly begin affecting tens of thousands.
DrRich hopes that overweight patients and their doctors will exercise restraint, and hold off on using this drug until we accumulate enough experience to truly understand the risks. DrRich also hopes for world peace, an end to hunger, and no more hurricanes.
NOTE: An update of this article, with the latest information, is now available here.
By DrRich
At the recent American Heart Association Scientific Sessions 2004, new data were reported on the effectiveness of rimonabant for treating obesity. Rimonabant, an investigational drug from Sanofi-Aventis, is aimed at helping patients lose weight and quit smoking. Early trials with rimonabant have been promising. ( Read about these earlier weight loss and smoking cessation trials here.)
In this most recent trial, the RIO-North America trial, 3040 patients were randomized to receive either placebo or one of two doses of rimonabant (5 mg or 20 mg per day.).
Patients taking 20 mg rimonabant had significant weigh loss, decrease in waist circumference, improved insulin sensitivity, and increases in HDL cholesterol, compared to patients on placebo. (Those taking 5 mg also had more weight loss than placebo patients, but the magnitude of weight loss was much less.) These results were strikingly similar to those previously reported in the RIO-EUROPE trial.
In this trial, however, patients who took 20 mg rimonabant for 1 year were then re-randomized to either continue on rimonabant, or to switch to placebo. Patients who stayed on rimonabant for the second year maintained the same degree of weight loss (they did not lose additional weight,) while those switched to placebo gained weight. At the end of 2 years, patients who took rimonabant for one year and placebo for the second year had about the same amount of overall weight loss as patients who took placebo from the beginning.
Side effects included depression, anxiety and nausea. About 1 in 8 patients taking rimonabant dropped out of the study due to side effects.
Is there a dark side to rimonabant?
From the data that continues to accumulate, it appears that "so far so good" is the watchword with rimonabant. However, several observers at the AHA meeting urged caution. There are two very good reasons not to get too excited about this drug just yet. First, rimonabant is the first of a new class of drugs targeting the endocannabiniod system, which helps to regulate pleasure, relaxation, and pain tolerance. We still do not have a good notion of what happens when we interfere with this system on a very long-term basis (and from this new study, it seems obvious that treatment with rimonabant will have to be chronic.) The fact that significant depression was seen in at least some of the patients enrolled in the trials so far ought to raise a fair amount of caution. Further, neurologists point out that the endocannabinoid system helps to protect the brain under some circumstances (such as stroke and head injury,) and some worry that brain damage in these circumstances might be worse in patients taking drugs that block the endocannabiniod system. Even more scary, a recent article in the journal Multiple Sclerosis describes a patient whose previously subclinical case of multiple sclerosis became active when this drug was started.
The second reason not to get overly excited yet is that, while rimonabant has now been used in a few thousand patients, once it is market released its usage will explode to the hundreds of thousands or even millions of patients. (Judging from the volume of e-mails DrRich gets each time he writes about this drug, the pent-up demand is massive.) Once this happens, any disturbing side effects that now seem infrequent (or that haven't even been identified yet) may suddenly begin affecting tens of thousands.
DrRich hopes that overweight patients and their doctors will exercise restraint, and hold off on using this drug until we accumulate enough experience to truly understand the risks. DrRich also hopes for world peace, an end to hunger, and no more hurricanes.
NOTE: An update of this article, with the latest information, is now available here.
