The WHO, governmental and health agencies have publicised the global obesity epidemic, affecting children, adolescents and adults, as one of the principal health concerns facing the world’s population today. Indeed, by 2025, the WHO estimates that obesity will emerge as a more serious world problem than malnutrition. Obesity is defined as a condition of abnormal or excessive fat accumulation and increases the risk of developing type II diabetes, coronary heart disease, hypertension, osteoarthritis and some cancers. The fundamental cause of obesity is the excess of energy intake over energy expenditure. Classification of obesity is determined through measurement of the body mass index (BMI), which is calculated by dividing body weight (kg) by height squared (m2). A value in excess of 30 indicates that the patient is obese.
It is estimated that over 250 million people suffer from obesity worldwide. The US has the greatest prevalence of obesity with up to 35% of the population defined as obese, and 54% defined as overweight. The UK has one of the highest rates of obesity in Europe, with 20% of the population defined as obese and over 50% defined as overweight. The development of safe and effective therapeutic interventions is imperative, with the aim to achieve weight losses which can be sustained sufficiently to reduce major health risks. One of the effective means to help loss of weight, as part of a comprehensive programme, is to prescribe drug treatments designed specifically to reduce appetite and food consumption, without significant side-effects.
At present, drug treatment for obesity is limited to three products that have entered the market. Orlistat is a lipase inhibitor that works by preventing the breakdown and absorption of fat in the intestinal system. However, its use is limited by gastrointestinal side effects. Sibutramine is a serotonin-noradrenaline reuptake inhibitor that influences brain mechanisms of satiety; however, the drug also affects the cardiovascular system, which limits its utility. Rimonabant is a cannabinoid CB1 receptor antagonist that acts on brain mechanisms of satiety and reward and which until recently was marketed in the UK and more than 40 other countries. However, the drug has not been approved for sale in the US due to FDA concerns about increased risk of depression and suicide and similar concerns have recently led the EMEA to recommend the suspension of the European marketing authorisation for rimonabant.