Sibutramine is a medicine used in people who are obese. It is mainly used to make patients feel drunk so that they don’t overeat and make it easier to lose weight.
In this article, we explain in more detail what sibutramine is, what are its effects and mechanism of action, contraindications and side effects, and clinical efficacy.
What is sibutramine and what effects does it have?
Sibutramine is an anorectic compound belonging to the group of amines (More precisely a tertiary amine) used for the treatment of obesity, because the main effect it produces in the person who consumes it is that of a feeling of fullness which prevents the ingestion of excess food , thus facilitating weight loss.
Besides producing a satiating effect, sibutramine also causes an increase in thermogenesis, which is our body’s ability to generate heat, thus helping to reduce body weight.
This medication is indicated for the treatment of obese people with a body mass index (BMI) greater than 30 kg / m²; that is, people with obesity type I and above (type II, type III or morbid and type IV or extreme). Again it can also be prescribed in case of overweight in people with a BMI equal to or greater than 27 kg / m²In this case, the associated risk factors, such as diabetes, high cholesterol or hypertension, must coexist.
Sibutramine is a drug that should be used as part of an obesity treatment program that includes guidelines for changing eating habits and increasing physical activity.
Mechanisms of action
Sibutramine is a compound which acts as a selective inhibitor of serotonin, norepinephrine and, to a lesser extent, dopamine reuptake. At the pharmacological level, this blocking of the absorption of monoamine neurotransmitters results, as we have seen, by a set of effects which essentially 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 in the synaptic levels of norepinephrine and serotonin at the central level, which allows the activation of the adrenergic receptors a1 and b1 (norepinephrine) and the 5-HT2A and 5 receptors. – Serotonergic HT2C (serotonin), mechanisms involved in the early activation of satiety mechanisms.
As for the thermogenic effects, they seem to be more specifically linked to the activation of beta 3 adrenergic receptors. On the other hand, sibutramine and its active metabolites have no activity on other receptors (Muscarinic, histaminergic or benzodiazepine), so that it does not induce side effects or pharmacological interactions with them.
Sibutramine is a drug that is contraindicated in people with 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, While breastfeeding and when other medicines such as nasal decongestants, antidepressants, cough suppressants and appetite suppressants are used.
Sibutramine should not be used, with a few exceptions, in people with a body mass index (BMI) less than 30 kg / m², or in children, adolescents or people over 65 years of age.
Although they are chemically related to amphetamine, the stimulating effects are less powerful and at the end of the treatment, there is no withdrawal syndrome. With all, the use of sibutramine is not free from side effects; the most common are:
- Dry mouth
- blushing of the face
- Increased blood pressure and heart rate
- Depressive symptoms (irritability, fatigue, anhedonia, etc.)
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 achieved and the dose of the drug, with the best risk-benefit 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 to a dose of 15 mg every 24 hours, without a significant increase in side effects.
Weight loss in the first 4 weeks of taking sibutramine is a good predictor patients who are 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 dose-proportional reduction in the used dose of the waist-to-hip ratio. Likewise, decreases the feeling of hunger and increases the effect of satiety in patients.
The Reductil controversy
In 2010, the Spanish Agency for Medicines and Health Products (AEMPS) ordered the withdrawal and preventive 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, at the time, considered that the expected benefit of this medicine did not outweigh its potential risks to the health of the patient.
Since its marketing, sibutramine has been associated with cases of patients reporting increases in blood pressure, heart rate and various side effects. In addition, its consumption was associated with several deaths in different European countries.
To check whether the use of this drug was really related to the incidence of these conditions and the death of these people, the large-scale SCOUT study was conducted, a randomized double-blind trial with a placebo group, which included 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 treated with sibutramine versus the placebo group.
With the findings of the study in hand, AEMPS urged doctors to stop prescribing or initiating new treatments with this drug, And pharmacists to stop distributing Reductil or to develop any other main formula with the active ingredient sibutramine.
- Bray, GA, Blackburn, GL, Ferguson, JM, Greenway, FL, Jain, AK, Mendel, CM, … and Seaton, TB (1999). Sibutramine causes dose-related weight loss. Obesity Research, 7 (2), 189-198.
- James, WPT, 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.