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. Its 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 < or = 30 mg for < or = 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 > or = 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 < or = 24 weeks' duration; data from longer trials are unavailable. Up to 15% of patients in < or = 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 pressor effects with sibutramine are reflected in the manufacturer's dosage and administration recommendations.
McNeely
W
W
Adis International Limited, Auckland, New Zealand.
Goa
K L
KL
D000818:Animals; D001067:Appetite Depressants / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic; D003503:Cyclobutanes / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002149:Energy Intake; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D009765:Obesity / Q000145:classification / Q000150:complications / Q000188:drug therapy*; D015431:Weight Loss / Q000187:drug effects
D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine