Sibutramine - A review of its contribution to the management of obesity

Sibutramine is an orally administered centrally acting weight management agent apparently devoid of amphetamine-like abuse potential. [ts primary (M2; BTS 54 505) and secondary (M1; BTS 54 354) amine metabolites are pharmacologically active and are thought to induce the natural processes leading to enhancement of satiety and thermogenesis by inhibiting serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (norepinephrine) reuptake. In clinical trials, once-daily sibutramine was administered at dosages of less than or equal to 30 mg for less than or equal to 24 weeks and 10 or 15 mg for 1 year in conjunction with reduced calorie intake, increased daily exercise and advice on eating behaviour. Dose-related bodyweight loss was greater with sibutramine than with placebo. Clinical effects were most commonly apparent at dosages greater than or equal to 10 mg/day. Weight loss of >1% within the first month of treatment appears indicative of good long term response with sibutramine. Weight loss was maintained during therapy for 1 year. longer term data are lacking. Weight regain occurred after treatment cessation in studies of less than or equal to 24 weeks' duration; data from longer trials are unavailable. Up to 15% of patients in less than or equal to 6-month studies did not respond to treatment irrespective of dose. Obese patients with type 2 (non-insulin-dependent) diabetes or hypertension lost significantly more mean bodyweight with sibutramine than with placebo, although weight loss was less than that in obese patients without comorbidities. The effect of sibutramine on mean fasting blood glucose levels and plasma lipid levels was unclear. Sibutramine, compared with placebo, statistically significantly increased blood pressure and heart rate in obese patients with or without hypertension when given for up to 12 months. However. after 12 weeks' treatment in hypertensive obese patients, diastolic blood pressure was reduced by similar amounts with sibutramine or placebo. Concerns over potential presser effects with sibutramine are reflected in the manufacturer's dosage and administration recommendations. Although long term tolerability data are scarce, Fooled data from 2952 patients in placebo-controlled trials (less than or equal to 1 year) revealed that the drug was generally well tolerated. The most commonly reported adverse events were headache, dry mouth, anorexia. insomnia and constipation. Echocardiographs indicated that sibutramine therapy (approximate to 8 months) did not adversely affect cardiac valve function in obese patients. Conclusion: Currently, there are few options for the long term management of obesity. Evidence although limited, suggests that in selected obese patients, sibutramine may be considered a useful adjunct to traditional nnnpharmacologi cal therapy, to effect a sustained moderate weight loss during treatment which is greater than that with placebo. Concerns over potential pressor effects of sibutramine may be allayed by careful patient selection and subsequent monitoring.