The article reviews the current pipeline of obesity pharmacotherapies, focusing on entero-pancreatic hormone-based treatments. Obesity is a chronic disease with significant health risks, and current treatments, such as GLP-1 receptor agonists (RA), have shown efficacy in weight loss (WL) and cardioprotection. Semaglutide 2.4 mg, a weekly injectable GLP-1 RA, results in 15–17% WL. Oral GLP-1 RA are under development and show similar efficacy. Newer combinations of entero-pancreatic hormones, such as tirzepatide (a dual GLP-1/GIP RA), have shown up to 22.5% WL in phase 3 trials. Other combinations, including cagrisema (GLP-1/amylin RA) and retatrutide (GLP-1/GIP/glucagon RA), are also in phase 3 trials and may offer greater WL. Agents with different mechanisms, such as bimagrumab, are in early trials and may improve body composition during WL. The new era in obesity pharmacotherapy aims to achieve WL levels similar to bariatric surgery. However, challenges remain, including treatment response variability, adverse events, and ensuring equitable access. New treatments may offer individualized care, but their long-term safety and efficacy need further study. Cardiovascular outcomes are also being evaluated, with semaglutide showing benefits in reducing major adverse cardiovascular events. The article highlights the potential of new pharmacotherapies to improve obesity management, but also emphasizes the need for research on long-term safety, cost-effectiveness, and equitable access.The article reviews the current pipeline of obesity pharmacotherapies, focusing on entero-pancreatic hormone-based treatments. Obesity is a chronic disease with significant health risks, and current treatments, such as GLP-1 receptor agonists (RA), have shown efficacy in weight loss (WL) and cardioprotection. Semaglutide 2.4 mg, a weekly injectable GLP-1 RA, results in 15–17% WL. Oral GLP-1 RA are under development and show similar efficacy. Newer combinations of entero-pancreatic hormones, such as tirzepatide (a dual GLP-1/GIP RA), have shown up to 22.5% WL in phase 3 trials. Other combinations, including cagrisema (GLP-1/amylin RA) and retatrutide (GLP-1/GIP/glucagon RA), are also in phase 3 trials and may offer greater WL. Agents with different mechanisms, such as bimagrumab, are in early trials and may improve body composition during WL. The new era in obesity pharmacotherapy aims to achieve WL levels similar to bariatric surgery. However, challenges remain, including treatment response variability, adverse events, and ensuring equitable access. New treatments may offer individualized care, but their long-term safety and efficacy need further study. Cardiovascular outcomes are also being evaluated, with semaglutide showing benefits in reducing major adverse cardiovascular events. The article highlights the potential of new pharmacotherapies to improve obesity management, but also emphasizes the need for research on long-term safety, cost-effectiveness, and equitable access.