The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials

Obesity is a complex and chronic disease that raises the risk of various complications. Substantial reduction in body weight improves these risk factors. Lifestyle changes, including physical activity, reduced caloric ingestion, and behavioral therapy, have been the principal pillars in the management of obesity. In recent years, pharmacologic interventions have improved remarkably. The Semaglutide Treatment Effect in People with Obesity (STEP) program is a collection of phase-III trials geared toward exploring the utility of once-weekly 2.4 mg semaglutide administered subcutaneously as a pharmacologic agent for patients with obesity. All the STEP studies included diet and exercise interventions but at different intensities. This review paper aims to explore the impact of the behavioral programs on the effect of semaglutide 2.4 mg on weight loss. The results of the STEP trials supported the efficacy of high-dose, once-weekly 2.4 mg semaglutide on body weight reduction among patients with obesity with/without diabetes mellitus. Semaglutide was associated with more gastrointestinal-related side effects compared to placebo but was generally safe and well tolerated. In all the STEP studies, despite the varying intestines of the behavioral programs, weight loss was very similar. For the first time, there may be a suggestion that these behavioral programs might not increase weight reduction beyond the effect of semaglutide. Nevertheless, the importance of nutritional support during substantial weight loss with pharmacotherapy needs to be re-evaluated.