Abstract
Background
The increasing off-label use of glucagon-like peptide-1 receptor agonists, including Semaglutide and Tirzepatide, has generated significant clinical and ethical debate. Originally approved for Type 2 Diabetes, these agents are increasingly prescribed for weight management in individuals without diabetes. This shift reflects changing perceptions of obesity but raises concerns regarding safety, accessibility, and appropriate prescribing practices. This systematic review examines patterns, drivers, and implications of off-label use.
Methods
A systematic search of PubMed, Scopus, and Web of Science identified studies reporting prescribing trends and outcomes associated with off-label use. Eligible studies included observational studies, clinical reports, and database analyses. Selection, extraction, and quality assessment followed established frameworks. A narrative synthesis was employed due to heterogeneity.
Results
Findings indicate a substantial increase in off-label prescribing for weight loss among non-diabetic populations. This trend is driven by demonstrated efficacy, social influence, and growing demand for pharmacological obesity management. However, evidence highlights emerging concerns, including medication shortages affecting diabetic patients, variability in prescribing, and limited long-term safety data. Reported adverse effects were consistent with known drug profiles, though real-world data remain limited.
Conclusions
Off-label use of glucagon-like peptide-1 receptor agonists is expanding, reflecting therapeutic potential and unmet demand. Nevertheless, evidence underscores gaps in long-term safety, oversight, and equitable access. Clearer prescribing guidelines are required to balance innovation with patient safety and healthcare equity.
Key messages
• Rapid expansion of off-label GLP-1 agonist use for weight loss highlights high clinical demand but creates shortages for diabetic patients.
• Clearer prescribing guidelines and regulatory oversight are needed to ensure equitable access and long-term patient safety.