Novel Oral Anti-Obesity Agents: New Perspectives with Lorcaserin?

Excerpt

The incidence and prevalence of obesity is increasing worldwide due to changes in lifestyles, with a shift to less physical activity and an increase in caloric intake. This development has led to an increased burden on healthcare systems and societies, as obesity is associated with severe co-morbidities (e.g. type 2 diabetes mellitus, hypertension, dyslipidaemia, sleep apnoea and many more) often leading to invalidity and psycho-social problems. Furthermore, obesity is associated with an increased mortality [1, 2]. The treatment strategies for obesity include lifestyle modifications, either as a single strategy or in conjunction with pharmacological treatments [3]. In recent years, different methods of bariatric surgery have also gained importance for the treatment of obesity [4‐6], although surgery is unlikely to solve the widespread obesity problem. Since lifestyle modifications are often ineffective and difficult to implement, pharmacological treatment of obesity seems very attractive. There are limited options for medical therapy of obesity at present; in most countries, only orlistat (a lipase inhibitor) is available as oral medication. Sibutramine (an amphetamine derivative) and rimonabant (a cannabinoid receptor blocker) have been removed from the market due to the increased cardiovascular risk associated with sibutramine and the association of depression, anxiety and suicidal ideation with rimonabant [7‐9]. Glucagon-like-peptide (GLP)-1 receptor agonists also have potential as weight-loss agents, but so far they are only approved for the treatment of type 2 diabetes and not yet for obesity. Apart from that, they are injectable agents [10, 11], and gastrointestinal adverse events (fullness, nausea, vomiting or diarrhoea) occur in approximately 20–30 % of patients, although usually only transiently at the initiation of therapy [11]. In this context, the development of novel oral anti-obesity agents seems necessary and prudent. …