By LIM WEY WEN The Star, Sunday January 31, 2010
The fate of a weight-loss drug hangs in the balance as world health authorities weigh its benefits against its risks.
GOING by the sheer number of diet pills available in the market, it seems many of us find it hard not to be attracted to the promise of a quick fix, particularly where weight loss is concerned.
You know the drill, because their advertisements won’t let you forget. “Who needs diets and exercise? Take a pill a day and watch the pounds melt away!”
We must keep reminding patients that they must continue with the diet and physical therapy although we add in the drug.
True to their word, some of these pills do help you lose weight fast. However, some can also give you palpitations, high-blood pressure, depression, insomnia, uncomfortable cramps.
And when these undesirable effects shows signs of being life-threatening, the product gets investigated and sometimes withdrawn if there is enough evidence to prove that the health risks outweigh the benefits of weight loss.
One pill down
On Jan 21, 2010, obesity drugs containing the active ingredient sibutramine, a chemical compound that makes people feel full and eat less by increasing the levels of two neurotransmitters in the brain (serotonin and noradrenaline), faced the possibility of being taken off the shelves.
Following reports of sibutramine-related deaths due to cardiovascular disease and the preliminary results of the SCOUT (Sibutramine Cardiovascular Outcome Trial) study, the European Medicines Agency (EMA) has recommended physicians and pharmacists Europe-wide to stop selling all products that contain sibutramine. This includes capsules containing sibutramine under the trade name Reductil (in Malaysia) as well as generic medicines.
On the same day, the US Food and Drug Administration had also asked Abbott, the maker of Reductil, to include a history of cardiovascular disease as a new contraindication to Reductil’s label yesterday in addition to the information included in its package insert.
In countries outside the EU, the response to the EMA and FDA’s recommendations are mixed. Qatar, Jordan, and Bahrain have subsequently banned the drug in their countries, while countries like India and Malaysia have chosen to warn the public and their physicians as they monitor the situation for future regulatory actions.
Until more data is made available in March, these decisions have been made based on the preliminary results of the Abbott-sponsored SCOUT study, an approximately 10,000 patient, six-year study to evaluate cardiovascular safety in patients who have known cardiovascular disease or at high risk for cardiovascular problems.
Among these patients, who are all above 55 years old and have a history of cardiovascular disease, diabetes or both, 11.4% had a heart attack or stroke compared to 10% of those who received placebos instead.
While Abbott has respected the EMA’s decision by suspending its marketing of sibutramine in Europe, it says in its press release that its products remain available in all other countries outside EU. “The company believes that there are many patients who benefit from sibutramine and respectfully disagrees with the committee’s recommendation to suspend the medicine.”
As it is, sibutramine is already inadvisable in patients with a history of any heart disease and inadequately controlled hypertension.
“More than 90% of patients in the SCOUT study were ineligible to receive sibutramine under current labeling, and none were managed according to labeling guidance – which recommends the medication be used for one to two years (instead of treatment for up to six years in SCOUT) and requires the patients to stop therapy if they do not respond to treatment (instead of continuing on sibutramine without experiencing adequate weight loss, as was done in SCOUT),” says Abbott in its press statement.
But why run a study to test a group of subjects that, in the first place, is advised not to receive the drug under normal circumstances, for a duration that greatly surpasses the recommended cut-off?
Abbott’s Director of Communications and Government Affairs Pamela Harrison only had this to offer: “The study was requested by the European regulatory authorities as a post-marketing commitment to evaluate cardiovascular safety in high risk patients. Throughout the course of the six-year study, the independent Data Safety Monitoring Board (DSMB) regularly reviewed safety data, and is determined that the study should continue.”
If that is Abbott’s way of saying that the data may not indicate the risks to the current patient group (who, if treated according to the label recommendations, must not have a history cardiovascular diseases), the EMA seems to think otherwise.
It announced, “The (EMA’s) Committee for Medicinal Products for Human Use (CHMP) noted that the use of sibutramine was not in accordance with the prescribing information for most of the patients enrolled in the SCOUT study ... However, because obese and overweight patients are likely to have a higher risk of cardiovascular events, the Committee was of the opinion that the data from SCOUT is relevant for the use of the medicine in clinical practice.”
Clearing the air
While the jury is still out whether sibutramine is dangerous even to those who are obese without heart disease or other risk factors, senior consultant endocrinologist and Malaysian Endocrine and Metabolic Society president Dr Nor Azmi Kamaruddin is not surprised by the results of the study.
“To be fair, it is already stated in the patient information sheet that this drug should not be used in patients who have cardiovascular disease,” he says. “Because what it does is increase your heart rate and basal metabolic rate in addition to suppressing appetite,” he explains. So it is expected – you may feel your heart pounding away as it pumps harder and faster, while your blood pressure may rise as a result of that. And for a person who already has a known or underlying heart disease, these changes can be fatal.
“That’s why we also do not prescribe for obese people who have heart disease or those who have high risk factors for developing heart disease – like when they are obese and diabetic,” he added.
Also, as sibutramine affects neurotransmitter levels in the brain and the central nervous system, you may also experience insomnia and anxiety as well. You can also experience mood swings, dry mouth and nausea as the neurotransmitter levels change.
This is why doctors do not prescribe this medicine to people who have psychiatric conditions. “Theoretically, due to its effect on the brain, it may worsen any psychiatric disorder, especially mania or psychosis,” said Dr Nor Azmi.
Currently, there are nine products containing sibutramine registered in Malaysia and all products carry these warnings and precautions in their product inserts, as directed by the Drug Control Authority. In 2006 alone, 6,000 Malaysians were prescribed the drug. Worldwide, 30 million patients have used it since 1997.
When used properly, sibutramine is effective in helping people lose weight, Dr Nor Azmi explains.
“Doctors usually prescribe drugs like sibutramine to help obese people who failed to lose at least 5% of body weight after six months on diet and physical therapy. “We do not use drugs as the first form of treatment, unless the patient has obesity and multiple risk factors where there is a need to bring down weight quickly,” he says.
However, he adds, when they are used, they are meant to be used as an addition to their diet and exercise regime rather than a replacement, for only a short term (between six months and two years).
But the problem is most patients want an easy way out, and that’s usually the reason they want to take these medications, Dr Nor Azmi says. ”That’s why I often tell my patients, ‘you got fat because of 20 years of bad eating habits, and you want to lose weight within one week. That’s just not possible.’
“The whole idea is to emphasise diet and physical therapy. We must keep reminding them that they must continue with the diet and physical therapy although we add in the drug.
“When they might not have lost as much weight with diet and exercise alone, they might lose more weight with the drug, and that gives them motivation to carry on. After six months, the doctor will stop the drug and they are supposed to continue with their diet and exercise.”
While waiting for additional data to complete its safety review in March, the FDA has advised patients who are currently using sibutramine to talk with their doctors to determine whether they should continue using the drug.
But if you are using sibutramine despite having heart disease or diabetes and other risk factors, Dr Nor Azmi urges you to see your doctor as soon as possible. “You may have been prescribed the medication wrongly,” he said.
Unfortunately, if over-the-counter slimming products are adulterated with sibutramine, there is no way to tell whether they contain the substance.
If you experience similar side effects of appetite suppressant drugs like sibutramine – palpitations, dry mouth, insomnia and anxiety – after consuming any slimming product, it may be wise to consider other alternatives.
The only sure way is to be vigilant and avoid these products as much possible, says Dr Nor Azmi.
