Approach to the Patient: Clinical Outcomes and Interim Strategies Following Discontinuation of Incretin Agonists

The global rise in obesity has led to an increasing need for pharmacologic therapies as adjuncts to lifestyle interventions for weight management. While obesity medications produce meaningful weight loss (∼5-24%) and improve cardiometabolic health, up to half of patients discontinue treatment within 1-2 years due to side effects, limited access, cost, or inadequate response. Discontinuation of obesity medications, however, often results in weight regain and reversal of associated health benefits, posing significant clinical challenges. Understanding the outcomes following cessation of pharmacotherapy and identifying effective interim strategies are essential to maintaining progress in weight management and minimizing long-term health risks. This approach to the patient article demonstrates two cases of patients in the real world setting who experience disruption of their obesity regimen with either a blunted response to reintroduction of therapy and/or weight regain and outlines practical approaches to mitigate weight regain and sustain health improvements long-term in patients with obesity.