Pharmacotherapy for obesity: moving towards efficacy improvement

Obesity is a chronic, recurring, progressive disease and a major public health problem associated with several other diseases that lead to disability, morbidity, and mortality. The prevalence of obesity has increased at pandemic levels, along with increasing weight-related comorbidities and deaths worldwide. Lifestyle interventions alone provide clinically significant long-term weight loss in only a small proportion of individuals, and bariatric surgery is not suitable or desirable for all patients. Historically, anti-obesity medications achieved a mean efficacy with weight loss between 5 and 10%, which significantly impacted several comorbidities and risk factors, but the average efficacy of these medications remained lower than that expected by both patients and health care professionals and eventually curbed long-term use. Moreover, there is no direct evidence on the impact of anti-obesity medications on cardiovascular outcomes. Semaglutide is a newer anti-obesity medication that changes the overall landscape, as phase 3 studies show a mean weight loss near the 15% threshold and significant proportions of patients with a weight loss of greater than 20%. In this review, we focus on the currently available anti-obesity medications, discuss the results of semaglutide, and present perspectives on the future of obesity treatment after semaglutide.