Sibutramine: Uses and Side Effects of This Drug

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

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

• Related article: "Obesity: psychological factors involved in being overweight"

What is sibutramine and what effects does it produce?

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

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

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

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

Action mechanisms

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

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

With regard to 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, histaminergic or benzodiazepine), so it would not induce side or pharmacological effects in interaction with them.

• You may be interested: "Norepinephrine (neurotransmitter): definition and functions"

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.

They should also refrain from consuming this drug people with heart disease, eating disorders (such as anorexia nervosa or bulimia), pregnant women, during breastfeeding and when using other drugs such as nasal decongestants, antidepressants, cough suppressants and appetite suppressants.

Sibutramine should not be used, with few exceptions, in people with a body mass index (BMI) lower than 30 kg / m², or in children, adolescents or people over 65 years of age.

Side effects

Despite being chemically related to the amphetamine, the stimulant effects are less potent, and withdrawal symptoms do not occur when treatment is stopped. With everything, the consumption of sibutramine is not exempt from generating side effects; the most common are the following:

• Dry mouth
• Facial blush
• Increased blood pressure and heart rate
• Sickness
• 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 hyperlipidaemia), have suggested that there is a direct relationship between the loss of weight obtained and the dose of the drug, the one with the best benefit-risk ratio being 10 mg every 24 hours.

However, there is a significant percentage of patients who do not respond adequately to a dose of 10 mg, but yes to one of 15 mg every 24 hours, without a relevant increase in the effects secondary.

Weight loss during the first 4 weeks taking sibutramine is a good predictor 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 studies, with the consumption of sibutramine there is also a statistically significant and proportional to the dose used reduction of the ratio between waist and hip. In addition, decreases the feeling of hunger and increases the effect of satiety in patients.

• You may be interested: "Types of psychostimulants (or psychoanalleptics)"

The Reductil controversy

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

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

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

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

With the findings of the study in hand, the AEMPS urged doctors to stop prescribing or starting new treatments with this drug, and to pharmacists to stop dispensing Reductil or to prepare any other magisterial formula with the active principle 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 randomized trial. The Lancet, 356 (9248), 2119-2125.