Obesity is a major public health issue with an increasing prevalence worldwide. Excess body fat is associated with various comorbidities, as well as increased overall mortality risk. The benefits of
weight loss are evident by the reductions in morbidity and mortality. The foundation for most weight loss programs involves strict lifestyle modification, including dietary change and exercise. Unfortunately, many individuals struggle with
weight loss and chronic weight management due to difficulty adhering to long-term lifestyle modification and the metabolic adaptations that promote weight regain. The use of adjunctive
pharmacotherapy has been employed to help patients not only achieve greater
weight loss than lifestyle modification alone but also to assist with long-term weight management. Historically,
antiobesity drugs have produced only modest
weight loss and required at least once daily administration.
Glucagon-like peptide-1 (GLP-1), a
hormone with significant effects on
glycemic control and weight regulation, has been explored for use as adjunctive
pharmacotherapy for
weight loss.
Semaglutide, a
GLP-1 receptor agonist, was recently approved by the Food and Drug Administration for chronic weight management in adults with
obesity or who are
overweight. The approval came after the publication of the
Semaglutide Treatment Effect in People with
Obesity clinical trials. In these 68-week trials,
semaglutide 2.4 mg was associated with significantly greater
weight loss compared to placebo.
Semaglutide differs from other
GLP-1 receptor agonists by having a longer half-life and producing greater
weight loss. This article provides an overview of the discovery and mechanism of action of
semaglutide 2.4 mg, and the clinical trials that led to its approval.