Sibutramine: uses and side effects of this drug

Sibutramine is a drug used mainly in cases of obesity. Let's see how it is.

Sibutramine is a drug used in people suffering from obesity.. It is mainly used to generate in patients the feeling of being satiated, so that they do not eat more than they should and it facilitates weight loss.

In this article we explain in more detail what sibutramine is, its effects and mechanism of action, contraindications and side effects, and its clinical efficacy.

What is sibutramine and what are its effects?

Sibutramine is an anorectic compound belonging to the amine group. (specifically a tertiary amine) used for the treatment of obesity, since the main effect it produces in the person who consumes it is a feeling of satiety that prevents excess food intake, thus facilitating weight loss.

In addition to producing a satiety effect, sibutramine also causes an increase in thermogenesis, which is our body's capacity to generate heat, thus contributing to the reduction of body weight.

This drug is indicated in the treatment of people with obesity and a body mass index (BMI) greater than 30 kg/m²; that is, individuals with type I obesity and above (type II, type III or morbid and type IV or extreme). Although it can also be prescribed in cases of excess weight in individuals with a BMI equal to or greater than 27 kg/m², in which case there must be coexistence of a BMI of at least 27 kg/m².in which case there must be associated risk factors such as diabetes, high cholesterol or hypertension.

Sibutramine is a drug that should be used in the context of an obesity treatment program that includes guidelines for the modification of dietary habits and increased physical activity.

Mechanisms of action

Sibutramine is a compound that acts as a selective inhibitor of serotonin, noradrenaline and, to a lesser extent, dopamine reuptake.. At the pharmacological level, this blocking of the reuptake of monoamine neurotransmitters translates, as mentioned above, into a set of effects which basically involve: an early feeling of satiety (which reduces food intake); and an increase in energy expenditure (thermogenesis).

The effects produced by sibutramine are related to the increase of synaptic levels of noradrenaline and serotonin at the central level, which allows the activation of the a1 and b1 adrenergic receptors (for noradrenaline) and the 5-HT2A and 5-HT2C serotonergic receptors (for serotonin), mechanisms involved in the early activation of satiety mechanisms.

Regarding thermogenic effects, these seem to be more specifically related to the activation of beta 3 adrenergic receptors. On the other hand, sibutramine and its active metabolites lack activity on other types of receptors (muscarinic, histaminic, histamine). (muscarinic, histaminergic or benzodiazepine), so it would not induce side or pharmacological effects in interaction with them.

Contraindications

Sibutramine is a drug that is contraindicated in people who have a history of type 2 diabetes mellitus with another associated risk factor, such as hypertension or high cholesterol.

The following people should also refrain from taking this drug people with heart disease, eating disorders (such as anorexia nervosa or bulimia), pregnant women, during lactation, and during the breastfeeding period.Sibutramine should also not be used during breast-feeding and when using other drugs such as nasal decongestants, antidepressants, cough suppressants and appetite suppressants.

Sibutramine should also not be used, with few exceptions, in people with a body mass index (BMI) of less than 30 kg/m², nor in children, adolescents or people over 65 years of age.

Side effects

Despite being chemically related to amphetamine, the stimulant effects are less potent and withdrawal syndrome does not occur when stopping treatment. Nevertheless, the use of sibutramine is not free of side effects.The most common side effects are the following:

• Dry mouth
• Facial flushing
• Increase in Blood Pressure and heart rate
• Nausea
• Insomnia
• Headache
• Depressive symptoms (irritability, tiredness, anhedonia, etc.)

Clinical efficacy

Research conducted with sibutramine in obese patients without or with concomitant pathologies (mainly type 2 diabetes, hypertension and hyperlipemia), have suggested that there is a direct relationship between the weight loss obtained and the dose of the drug, with the best benefit/risk ratio being that of 10 mg every 24 hours.

Nevertheless, there is a significant percentage of patients who do not respond adequately to a dose of 10 mg, but do respond to a dose of 15 mg every 24 hours, without a significant increase in side effects.

Weight loss during the first 4 weeks on sibutramine is a good predictor of patients who will be more likely to benefit from long-term treatment. of patients who will be more likely to benefit from long-term treatment. The maximum weight reduction occurs at 3 months, which is maintained during the treatment period.

According to the studies, with sibutramine consumption there is also a statistically significant and dose-proportional reduction in waist-to-hip ratio. It also also decreases the sensation of hunger and increases the satiety effect in patients.

The Reductil controversy

In 2010, the Spanish Agency of Medicines and Medical Devices (AEMPS) ordered the withdrawal and precautionary suspension of the sales of sibutramine, marketed in Spain under the name Reductil. This decision was taken on the recommendation of the European Medicines Agency, which at the time considered that the expected benefit of this drug did not outweigh its potential risks to patient health.

Since its commercialization, sibutramine had been associated with cases of patients reporting increases in blood pressure, heart rate and various adverse reactions. In addition, its use was associated with several deaths in different European countries.

To test whether the use of this drug was really related to the incidence of these pathologies and to the deaths of these individuals, the large-scale SCOUT study was carried out, a randomized, double-blind, placebo-controlled trial involving 10,000 obese or overweight patients with cardiovascular disease (CVD) and/or type 2 diabetes mellitus and with at least one additional risk factor for CVD.

After a 5-year follow-up, the results of the study showed an increased risk of serious cardiovascular events (such as myocardial infarction and stroke) in the group of patients (such as myocardial infarction and stroke) in the group of patients treated with sibutramine versus the placebo group.

With the conclusions of the study in hand the AEMPS urged physicians to stop prescribing or initiating new treatments with this drug, and pharmacists to stop prescribing or initiating new treatments with sibutramine.and pharmacists to stop dispensing Reductil or preparing any other master formula with the active ingredient sibutramine.

Bibliographic references:

• Bray, G. A., Blackburn, G. L., Ferguson, J. M., Greenway, F. L., Jain, A. K., Mendel, C. M., ... & Seaton, T. B. (1999). Sibutramine produces dose-related weight loss. Obesity Research, 7(2), 189-198.
• James, W. P. T., Astrup, A., Finer, N., Hilsted, J., Kopelman, P., Rössner, S., ... & STORM Study Group. (2000). Effect of sibutramine on weight maintenance after weight loss: a randomised trial. The Lancet, 356(9248), 2119-2125.