Bariatrics and endoscopic therapies for the treatment of metabolic disease: Past, present, and future

The burden of chronic metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) and the urgency of the epidemiological situation necessitate the development of therapies that enhance metabolic health and alter the trajectory of metabolic disease in society. Certain bariatric-metabolic surgeries have proven to be effective approaches for treating metabolic dysfunction, showing remission or significant improvements in obesity, T2DM, and MASLD-related outcomes, suggesting that these interventions might be able to "reset" a pathologically calibrated metabolic setpoint. However, considering the challenges and invasiveness of surgery, endoscopic bariatric metabolic therapies (EBMTs) have emerged with a primary focus to reconstruct or mimic anatomical and/or functional changes observed with bariatric surgery in a more broadly accessible manner. These innovative approaches offer a potentially promising solution to address significant unmet medical need in the large segment of society, which remains at risk for the consequences of metabolic diseases. In this review, we discuss therapeutic options within the EBMT space in the context of the metabolic setpoint intellectual model and provide a brief overview of current knowledge surrounding their mechanisms of action and impact on metabolic health. Finally, we explore future perspectives and directions in this exciting field.