Advancements and challenges in the management of obesity using pharmacotherapy (Review)

Obesity is a chronic, recurrent and progressive disease that is a major public health issue, contributing to disability, morbidity and mortality worldwide. The global increase in obesity prevalence has been accompanied by an increase in weight-related comorbidity and mortality rates. To address this growing public health issue, the development and use of anti-obesity medications (AOMs) have escalated in recent years. The present review aims to discuss the most recent information on AOMs and the health effects of their regular use. The gastrointestinal (GI)-hypothalamic axis has been revealed to play a key role in the regulation of food intake and energy expenditure, which has led to the development of AOMs to target peptides secreted from the GI tract, including glucagon-like peptide-1 (GLP-1). GLP-1 receptor agonists are among the most widely investigated drugs in the rapidly developing field of hormone-based AOMs. However, most GLP-based drugs cause undesirable side effects. A promising approach to combat cardiometabolic conditions, including diabetes and obesity, is to reduce food consumption while also raising energy expenditure. Notably, novel candidate anti-obesity drugs have been shown to activate neurokinin 2 receptors (NK2Rs) in mice, leading to appetite suppression without the side effects observed with previous generations of treatments. However, additional research is necessary to address the side effects associated with AOMs, particularly those affecting the GI tract, gallbladder and pancreas. Furthermore, the potential of NK2R activation merits investigation in clinical trials, particularly in high-risk patients.