A Lineup for Next Anti-Obesity Medicines: Beyond Incretin-Based Pharmacotherapy

Background/Objectives: Obesity is a chronic and multifactorial disease, and the global prevalence of obesity-induced metabolic and systemic complications is expected to rise. Current peptide-based drugs that mainly target glucagon-like peptide-1 receptor activation have shown unprecedented efficacy in body weight reduction. Nevertheless, they show undesirable adverse effects including gastrointestinal effects, lean mass reduction, and rebound weight gain after ending pharmacotherapy. These underscore the medical need for additional anti-obesity drugs with novel pathways. Methods: Literature updating current anti-obesity pharmacotherapy and reporting potential drug targets and candidates in the last five years was searched across PubMed. The resulting literature was classified into working mechanisms and target receptors. Results: Recent research on incretin-based peptide drugs has focused on developing more convenient regimens by introducing longer-acting once-monthly injection or oral formulation. Novel anti-obesity targets other than incretin receptors have also been suggested. This narrative review summarizes recent research updates on peptide-based drugs and upcoming anti-obesity drug candidates tested in clinical and in vivo studies. Conclusions: Beyond the current peptide-based pharmacotherapy, novel anti-obesity drug candidates are waiting for further validation in clinical trials. When used alone or combined with the available drugs, these candidates may produce more effective and safer pharmacotherapy for obesity treatment.