Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
10 mg and 15 mg capsules
Approved indication: obesity
Australian Medicines Handbook Section 12.10
Drugs are not the first-line treatment for people who are overweight (see 'Obesity and its management', Aust Prescr 1999;22:12-6). Sibutramine can be considered for obese patients who are unable to reduce their weight despite changing their diet and taking more exercise. It should only be considered if the patient's body mass index is at least 30 kg/m2 (27 kg/m2 if there are other risk factors such as hypertension or diabetes).
Although depression is not an approved indication, sibutramine is a serotonin reuptake inhibitor. It also inhibits the reuptake of noradrenaline and dopamine. Sibutramine is structurally related to amphetamine and is mainly thought to act through its amine metabolites.
After its rapid absorption sibutramine undergoes extensive first-pass hepatic metabolism. As cytochrome P450 3A4 is involved in the metabolism there is a potential for interactions with drugs which induce (e.g. phenytoin) or inhibit(e.g. erythromycin) this enzyme. The active metabolites have a half-life of14-16 hours and are also eliminated by metabolism.
Patients start treatment with a daily dose of 10 mg. If they have lost less than 2 kg after four weeks, the dose can be increased to 15 mg daily. Treatment should stop if the patient has not lost 5% of their weight after three months. Weight loss in patients with diabetes is slower so they can have a six month trial of treatment.
The maximum weight loss usually occurs after six months treatment. Approximately 60% of the patients who lose 2 kg in the first month of treatment will lose 5% or more of their body weight by six months.
In a double-blind trial 485 obese people were given dietary advice and took either sibutramine or a placebo. After a year 39% of the patients taking 10mg and 57% of the patients taking 15 mg had lost at least 5% of their bodyweight, compared with only 20% of those who took a placebo.1 Another study showed the importance of lifestyle modification. Women who just took sibutramine only lost 4.1% of their body weight after a year, whereas those who also modified their lifestyle lost 10.8% of their body weight. The weight loss was even greater if they also followed a diet.2
Sibutramine increases heart rate and blood pressure. Patients should therefore have their pulse and blood pressure checked at least every two weeks in the first three months of treatment and then at least once every three months. A sustained rise in heart rate of 10 beats/minute or a 10 mmHg increase in blood pressure are indications for stopping treatment. A history of coronary or cerebrovascular disease contraindicates sibutramine. Frequent adverse effects include loss of appetite, dry mouth, constipation and insomnia.
The options for the drug treatment of obesity are limited. Sibutramine does not seem to be a major advance. Although it produces statistically significant weight loss the clinical benefit of losing a few kilograms is questionable. In the year-long study the mean weight loss with 10 mg sibutramine was 4.4kg, only slightly greater than the weight loss of 1.6 kg in the placebo group.1 Although some patients who have responded to six months treatment have continued to take sibutramine for up to two years they do not continue to lose weight. The achieved weight loss is largely maintained while patients continue to take the drug, but they start to regain weight as soon as they stop.3 There is no information on the long-term effects of sibutramine on the mortality and morbidity of obesity.
- Smith IG, Goulder MA. Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity. J Fam Pract 2001;50:505-12.
- Wadden TA, Berkowitz RI, Sarwer DB, Prus-Wisniewski R, Steinberg C. Benefits of lifestyle modification in the pharmacologic treatment of obesity. Arch Intern Med 2001;161:218-27.
- James WPT, Astrup A, Finer N, Hilsted J, Kopelman P, Rössner S, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Lancet 2000;356:2119-25.