Obesity is a multifactorial, chronic disorder that has reached epidemic proportions in most industrialised countries and is threatening to become a global epidemic. Clinical management of obese patients is complex and serious doubts have arisen with regard to safety and efficacy of
drug therapy. Following the withdrawal of
fenfluramine and
dexfenfluramine in 1997, interest has focused on novel
anti-obesity drugs. Pharmacological approaches to the management of
obesity can, in broad terms, use different distinct strategies: firstly, to reduce energy intake; secondly, to increase energy expenditure; and thirdly, to alter the partitioning of nutrients between fat and lean tissue.
Sibutramine is a
serotonin-
noradrenaline (
norepinephrine) reuptake inhibitor indicated for the management of
obesity in conjunction with a reduced calorie diet. The pharmacological mechanisms by which
sibutramine exerts its
weight loss effect are likely due to a combination of reduced appetite, feelings of satiety and possibly the induction of thermogenesis. The efficacy of
sibutramine for inducing initial
weight loss and the subsequent maintenance of
weight loss is well proven in short- and long-term clinical trials of up to 2 years' duration. Most individual placebo-controlled trials and pooled estimates found that the
drug produced statistically significant greater
weight loss than placebo at all observed endpoints (weighted mean difference for weight change at 8 weeks: -3.4 kg; mean difference range for weight change at 6 months: -4.0 to -9.1 kg; and at 1 year: -4.1 to -4.8 kg). The most frequent dosage regimen in these trials was 10-20 mg daily. Findings suggested a dose-effect relationship in terms of
weight loss.
Sibutramine was also associated with better weight maintenance relative to placebo (statistically significant difference). Results from mainly small trials showed that
sibutramine produced more favourable outcomes in terms of loss of fat mass, reduction in body mass index and loss of > or = 5-10% of initial bodyweight. The most commonly reported adverse effects of
sibutramine are
headache,
constipation and
nausea. Certain adverse events associated with the nervous system, including
dizziness, dry mouth and
insomnia, are reported by > 5% of patients receiving
sibutramine. Increases in blood pressure and heart rate were possible adverse effects that require regular monitoring especially in obese hypertensive patients. Neither left-sided cardiac valve disease nor
primary pulmonary hypertension was associated with the use of
sibutramine. The assessment of the benefit-risk profile of
sibutramine remained positive, although the product must be kept under regular review.