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

Abstract

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][5][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][8][9]. Glucagon-likepeptide (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 antiobesity agents seems necessary and prudent.Recently, lorcaserin, a serotonin 5-HT 2C receptor agonist, has been approved in the USA for the treatment of obesity as an adjunct to lifestyle modifications in obese adults (body mass index [BMI] C30 kg/m 2 ), or overweight adults (BMI C27 kg/m 2 ) with at least one weight-related co-morbid condition (e.g. dyslipidemia, hypertension, type 2 diabetes). The approval has been based on a clinical study programme with lorcaserin that includes studies with a duration of 2 years. A comprehensive overview of this agent, including its clinical profile regarding efficacy and safety is given in the article by Hoy in this issue [17].The efficacy and safety of lorcaserin was investigated in large clinical trials , BLOSSOM [13] and BLOOM [18]), using doses of 10 mg lorcaserin twice daily in a randomized, multicentre, placebo-controlled, double-blind fashion. Significantly more patients receiving lorcaserin achieved a bodyweight reduction from baseline of C5 % and C10 % compared with the placebo group after 12 months. At 24 months, the least square mean bodyweight reductions from baseline (at ...

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