Off-label use patterns of glucagon-like peptide-1 receptor agonists: a systematic review
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.
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BibTeX
@article{ofodile2026offlabel,
title = {{Off-label use patterns of glucagon-like peptide-1 receptor agonists: a systematic review}},
author = {UF Ofodile and JC Nwadigo and CC Aghalu},
journal = {The European Journal of Public Health},
year = {2026},
month = oct,
doi = {10.1093/eurpub/ckag169.1303},
url = {https://doi.org/10.1093/eurpub/ckag169.1303},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Off-label use patterns of glucagon-like peptide-1 receptor agonists: a systematic review
AU - UF Ofodile
AU - JC Nwadigo
AU - CC Aghalu
PY - 2026
DA - 2026/10/01
JO - The European Journal of Public Health
DO - 10.1093/eurpub/ckag169.1303
UR - https://doi.org/10.1093/eurpub/ckag169.1303
AB - 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.
SN - 1101-1262
SN - 1464-360X
ER -