Semaglutide and tirzepatide have recently been approved for obesity and found to achieve ≥15% weight loss in clinical trials. These drugs have been referred to as second-generation medications because the unprecedented degree of weight loss they afford is sufficient to treat or prevent a broad array of obesity complications and related diseases. Many other medications are in development based on the actions of nutrient-regulated hormones (NRHs), including mono-, dual-, and triple-receptor agonists/antagonists for glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, amylin, peptide tyrosine-tyrosine, and glucagon. Clinical trial evidence is accumulating that these medications ameliorate multiple biomechanical, metabolic, and vascular complications of obesity. These tools enable a comprehensive complications-centric approach to care within the contextual framework of the diagnostic term adiposity-based chronic disease (ABCD). The potential to reduce patient suffering and the huge social burden of ABCD is profound. The current era of drug development based on NRHs could represent a landmark in the history of medicine provided that societies ensure access to these medications for the patients who need them.