Emerging Trends in Endoscopic Bariatric Therapies: Personalization Through Genomics and Synergistic Pharmacotherapy.

Obesity is a major global health challenge associated with significant metabolic and gastrointestinal comorbidities. While metabolic and bariatric surgery remains the gold standard for durable weight loss, the desire for additional options has fueled the development of endoscopic bariatric therapies (EBTs) as another tool for weight loss. This review examines established EBTs, including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGBs), and transoral outlet reduction (TORe), alongside emerging therapies such as duodenal mucosal resurfacing (DMR), incisionless anastomosis creation, and fully automated endoscopic gastric remodeling systems. ESG has demonstrated durable weight loss, favorable safety, and superior cost-effectiveness compared to pharmacotherapy alone, while combination strategies using EBTs and anti-obesity medications (AOMs), particularly GLP-1 receptor agonists, have resulted in greater total-body weight loss than either modality alone. Genetic variation, particularly within the leptin-melanocortin pathway, may predict response to endoscopic interventions and guide personalized treatment selection. Novel investigational procedures such as DMR, automated or robotic gastric remodeling, and magnetic or ultrasound-assisted gastric bypass show promising early results. Endoscopic therapies are poised to become increasingly central to the personalized, scalable management of obesity and related metabolic diseases.