Weight loss drugs: Sibutramine (Meridia)

The appetite is controlled by the area in the brain called the appetite center. The activity of the appetite center depends of various inputs, such as blood levels of glucose and fatty acids, as well as the overall biochemical state of the brain, particularly the levels of the key neurotransmitters, such as serotonin. For example, SSRI, the antidepressants that elevate the level of the neurotransmitter serotonin by blocking its recycling be neurons were found to reduce appetite in some patients.

Sibutramine (Meridia) was the first drug specifically developed for the purpose of appetite suppression by modulating the levels of neurotransmitters in the brain. In particular, sibutramine elevates the levels of neurotransmitters serotonin, norepinephrine and dopamine by blocking their reuptake (recycling) by neurons.

Sibutramine has been shown effective for weight loss. However, most studies to date have been relatively short-term (up to 12 month) and weight loss effects of the drug have been relatively modest. Depending on the study, the weight loss after up to 6-12 month on simutramine ranged from about 10 to 30 pounds (the range was about 3 - 20 pounds for placebo). Many researchers noted a significant variation in how well people respond to sibutramine. It appears that people who respond well in the first four weeks (i.e. those who lose about one pound per week) tend to achieve greater weight loss and maintain it better later on.

Sibutramine was also shown effective for weight maintenance as late as two years after the initial weight loss. In particular, researches noted the following:

Maintenance of weight loss with sibutramine was examined in a 2-year, double-blind, placebo-controlled trial. After a 6-month run-in phase in which all patients received sibutramine 10 mg (mean weight loss, 26 lbs.), patients were randomized to sibutramine (10 to 20 mg, 352 patients) or placebo (115 patients). The mean weight loss from initial body weight to endpoint was 21 lbs. and 12 lbs. for sibutramine and placebo patients, respectively. A statistically significantly (p<0.001) greater proportion of sibutramine treated patients, 75%, 62%, and 43%, maintained at least 80% of their initial weight loss at 12, 18, and 24 months, respectively, compared with the placebo group (38%, 23%, and 16%). Also 67%, 37%, 17%, and 9% of sibutramine treated patients compared with 49%, 19%, 5%, and 3% of placebo patients lost 5%, 10%, 15%, and 20%, respectively, of their initial body weight at endpoint. From endpoint to the post-study follow-up visit (about 1 month), weight regain was approximately 4 lbs for the sibutramine patients and approximately 2 lbs for the placebo patients.

Unfortunately, it is hard to predict in advance who is likely to have a greater response sibutramine. Furthermore, as with most existing weight loss drugs, even good responders would often see a decrease or even complete loss of effectiveness over the long term. Finally, like most drugs that interfere with the central nervous system, sibutramine has a sizeable list of side effects. In sibutramine studies, the most common side effects were dry mouth, anorexia, insomnia, constipation and headache. Less frequent side effects possibly related to sibutramine included anxiety, depression, dizziness and others.

Overall, one should balance the benefits of relatively modest weight loss on sibutramine (it is modest on average, some people lose a lot more than others) against side effects, costs and long-term uncertainties. People who opt to try sibutramine should keep in mind that it seems to work best in combination with cutting calories.

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