Sibutramine

What is Sibutramine?

The facts you need to know:

- Medicines containing sibutramine have been approved in the European Union (EU) since 1999.

- Sibutramine is a "serotonin-norepinephrine reuptake inhibitor" (SNRI).

- Medicines containing sibutramine are used to treat obesity.

- The increased levels of neurotransmitters in the brain help people feel full after a meal, which helps reduce their food intake.

Sibutramine was approved by the FDA in the USA in 1997. It is a serotonin-norepinephrine reuptake inhibitor that induces weight loss by increasing satiety and promoting energy expenditure. Sibutramine has also been shown to lower blood sugar and lipid levels. However, it has been reported that sibutramine could increase blood pressure due to its norepinephrine action, which would necessarily limit its use in patients with hypertension. Some recent studies suggest that sibutramine does not significantly increase blood pressure compared to a placebo.

No meta-analysis has been conducted on the effect of sibutramine on blood pressure, although a number of systematic reviews have demonstrated the weight-reducing effects of sibutramine. However, since obese patients often suffer from high blood pressure, we considered a systematic review of the effect of sibutramine on blood pressure necessary. The purpose of this study was to provide a comprehensive meta-analysis of randomized controlled trials of the effects of sibutramine on blood pressure and weight loss.

Sibutramine is a "serotonin-norepinephrine reuptake inhibitor" (SNRI). It prevents the neurotransmitters 5-hydroxytryptamine (also called serotonin) and norepinephrine from being reabsorbed into the nerve cells in the brain. Neurotransmitters are chemicals that allow nerve cells to communicate with each other. By blocking their reuptake, sibutramine increases the amount of these neurotransmitters in the brain.

Medicines containing sibutramine are used to treat obesity. The increased neurotransmitter levels in the brain help patients feel full after a meal, which helps reduce their food intake. They are used in addition to diet and exercise in obese (severely overweight) patients with a body mass index (BMI) of at least 30 kg/m² and in overweight patients (with a BMI of at least 30 kg/m²) up to 27 kg/ m²) and also have other risk factors associated with obesity, such as type 2 diabetes or dyslipidemia (abnormal levels of fat in the blood).

Medicines containing sibutramine have been approved in the European Union (EU) since 1999. They are available as capsules containing 10 mg or 15 mg of sibutramine under the trade names Reductil and other names (Afibon, Ectiva, Lindaxa, Meissa, Meridia, Minimacin, Minimectil, Obesan, Sibutral, Sibutril, Siluton, Sitrane, Redoxade, Zelixa and Zelium) and as generics.

Sibutramine is used for the treatment of obesity, including weight loss and weight loss maintenance, and should be used in conjunction with a calorie-restricted diet.

Why was sibutramine reviewed?

Sibutramine was originally reviewed by the agency in 1999 and 2002 because of concerns about its safety, particularly cardiovascular side effects (elevated blood pressure and heart rate). At that time, the CHMP concluded that the benefits of sibutramine in the treatment of obese and overweight patients outweighed the risks. However, the committee also called on Abbott Laboratories, which produces Reductil, to start a study of sibutramine in patients with cardiovascular risk factors, particularly to examine the drug's safety. The committee also asked the company to provide semi-annual updates on the progress of the study.

For this reason, in 2002 the company launched the SCOUT study (Sibutramine Cardiovascular Outcome Trial) to evaluate the effects of weight loss with sibutramine on cardiovascular problems in a large group of overweight and obese patients at high risk of cardiovascular disease to determine. The study compared sibutramine with placebo (a dummy treatment) and examined not only how much weight patients lost, but also the occurrence of cardiovascular events such as heart attack, stroke and cardiac arrest. In total, approximately 9,800 patients were followed up for six years.

Although the full data from the SCOUT trial have not yet been analyzed, the trial's Data Safety Monitoring Board (a panel of independent experts tasked with regularly reviewing the results of the clinical trial).

Sibutramine appears to be relatively well tolerated, with the most common side effects being dry mouth, insomnia and constipation. The biggest problem with sibutramine is its ability to increase blood pressure and heart rate. Although on average these changes are small, they can be quite significant. In some patients this may not be the case. It is therefore recommended that blood pressure and pulse be measured before starting therapy and monitored at regular intervals thereafter. It is also recommended not to use sibutramine in patients with coronary artery disease, heart failure, cardiac arrhythmias or a history of stroke. Given that many obese patients have concomitant cardiovascular disease, these warnings preclude the use of sibutramine in such obese patients.

Sibutramine effectively promotes weight loss. Weight loss with sibutramine is associated with both positive and negative changes in cardiovascular and metabolic risk factors. There is insufficient evidence to accurately determine the long-term benefit-risk profile of sibutramine.

Obesity is quickly becoming one of the biggest health problems in the United States. More than 64% of all U.S. adults were overweight or obese between 1999 and 2000 (defined as a body mass index [calculated as weight in kilograms divided by the square of height in meters] of 25).

1. The National Institutes of Health has issued guidelines for obesity treatment, which suggest that all obese adults (body mass index ≥30) and all adults with a body mass index of at least 27 and concomitant risk factors or diseases are candidates for are drug therapy.

2. Given these broad criteria, more than 100 million adults may be eligible for drug therapy for obesity in the United States.

1-3. The National Institutes of Health guidelines are based on a growing body of evidence linking obesity in adults with increased risk of several chronic diseases, reduced quality of life, and early mortality.

The recognized goal of weight loss is to prevent or reduce obesity-related morbidity and mortality by improving cardiovascular and metabolic risk factors.

4. Unfortunately, there is little evidence that available weight loss medications achieve this goal. Recently, safety concerns have outweighed evidence for the benefits of many weight loss medications.

5. Since 1997, five drugs have been withdrawn from the market worldwide due to inadequate documented efficacy and safety: fenfluramine hydrochloride, dexfenfluramine hydrochloride and phenylpropanolamine hydrochloride worldwide and diethylpropion hydrochloride and phentermine hydrochloride in Europe.

6-8. Following these withdrawals, sales of the remaining weight loss products have increased.

9. Introduced in 1997, sibutramine hydrochloride is a relatively new weight loss agent with a novel mechanism of action - it is a norepinephrine and serotonin reuptake inhibitor that can also stimulate thermogenesis.

10 It is approved for use worldwide at a dosage of 10 to 15 mg/day. Sibutramine has been shown to promote moderate weight loss, but concerns about cardiovascular side effects have limited its market penetration. In particular, in March 2002, the Italian regulatory authority temporarily suspended the marketing authorization of sibutramine, citing 50 adverse reactions, including two cardiovascular deaths.

11. The European Committee for Proprietary Medicinal Products and the Health Sciences Authority (UK) subsequently conducted independent reviews of sibutramine and concluded that the risk-benefit profile remains positive. These and other safety concerns have led a consumer group to petition against the drug, The Food and Drug Administration has banned the sale of sibutramine in the United States.

12. Despite these concerns, there have been no comprehensive systematic reviews of sibutramine since June 2000.

13. With this in mind, the aim of our systematic review was to assess the quality of published and unpublished evidence for sibutramine as a weight loss agent and to quantify its benefits and harms using a meta-analysis.

Sibutramine affects chemicals in the brain that affect weight maintenance.

Sibutramine is used along with diet and exercise to treat obesity, which may be related to diabetes, high cholesterol, or high blood pressure.

Do not use sibutramine if you have taken an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) in the last 14 days . If you take sibutramine before the MAO inhibitor has cleared your body, serious, life-threatening side effects may occur.

You should not take sibutramine if you are allergic to it, if you have severe or uncontrolled high blood pressure, an eating disorder (anorexia or bulimia), if you are taking stimulant diet pills, or if you have a history of coronary artery disease, stroke, or heart disease .

Before taking sibutramine, tell your doctor if you have glaucoma, high blood pressure, liver or kidney disease, depression, hypothyroidism, seizures, a bleeding disorder, or a history of gallstones, or if you are older than 65 or younger than 16 years.