Pharmacological treatment of obesity: present status

Abstract

OBJECTIVE: Obesity poses a serious health hazard and its treatment is often disappointing. This review describes the present status of pharmacological treatment of obesity in man.

DESIGN: Obesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. The mode of action, efficacy and safety of each approach will be briefly discussed.

RESULTS: All of the pharmacological possibilities have potential activities, but also serious limitations. While current anti-obesity pharmacotherapy essentially uses centrally-acting anorectic drugs, severe side-effects (more particularly pulmonary hypertension and valvular heart disease) have been reported, leading to the withdrawal of licensed fenfluramine and d-fenfluramine. New approaches have been recently proposed, such as sibutramine, an amine reuptake inhibitor which decreases food intake, and orlistat, an intestinal lipase inhibitor which decreases fat absorption.

Obesity is a chronic disease and should be treated as such with reasonable expectations. Large-scale one-year placebo-controlled studies demonstrated that d-fenfluramine, sibutramine and orlistat significantly increased body weight loss by an average of 2–4 kg when compared to placebo and, more interestingly, multiplied by 2–3 the number of patients who succeeded in obtaining and maintaining a reduction of more than 10% of initial body weight. Interestingly, some of these compounds may also exert favourable effects on other vascular risk factors, independently of weight loss.

CONCLUSIONS: Even if all anti-obesity pharmacological approaches can be helpful, they also have important limitations so that other strategies including either combined therapies or new drugs (peptides) are currently under investigation.