Therefore, particularly for these drugs, frequent updates are essential to accurately assess the drugs long-term benefits
Incretin therapies The first generation of weight-loss medications are incretin therapies that regulate insulin secretion, building on type 2 diabetes mellitus (T2DM) treatments utilising glucagon-like peptide-1 (GLP-1) receptor agonists
The clinical development program for orforglipron is among the most extensive in the history of obesity pharmacotherapy

These medications mimic the actions of the endogenous incretin hormone GLP-1 by enhancing glucose-dependent insulin secretion, suppressing glucagon release, delaying gastric emptying, and promoting satiety.[1] Incretin hormones also exert effects across multiple organ systems, including cardiovascular, renal, and skeletal systems.[1] Owing to these pleiotropic mechanisms, the clinical use of GLP-1RAs has expanded exponentially, both for diabetes and for a broadening spectrum of diseases and conditions.[2] Obesity plays a central role in the pathogenesis and progression of T2DM, yet many traditional glucose-lowering therapies are associated with weight gain.[3] The observation that GLP-1RAs not only improve glycemic control but also result in significant weight loss marked a paradigm shift in diabetes pharmacotherapy, prompting investigation into their therapeutic potential in individuals without diabetes to treat obesity and related comorbidities.[4] Subsequently, large-scale cardiovascular and kidney outcome trials have demonstrated additional benefits of GLP-1RAs, further supporting their use in high-risk populations independent of diabetes status.[4] These trials resulted in a rapid evolution of the clinical landscape for GLP-1RAs in the last decade, with growing evidence supporting their role in treating obesity, cardiovascular disease, chronic kidney disease (CKD), and other metabolic-related disorders.[520] This expansion reflects both their favorable efficacy profile and their broader physiological effects
