OBJECTIVES: GLP-1 agonists were initially developed for the management of type-2 diabetes (T2D). However, positive outcomes from clinical trials highlighted their potential for significant weight loss. Market entry led to off-label use for obesity management, sparking discussions among stakeholders due to implications on supply for T2D patients. This review assesses the timeline from European Medicines Agency (EMA) approval to the availability of injectable GLP-1 agonists for both indications in France and Spain, while also examining their real-world off-label use prior to official approvals.

METHODS: The EMA website was consulted to identify GLP-1s authorised for treating T2D and obesity. Subsequently, the websites of health technology assessment bodies (HTA) in France and Spain were reviewed to determine the time between EMA approval and positive recommendations within their healthcare systems. Additionally, Embase and Medline were searched for data on off-label use of GLP-1 agonists in European cohorts.

RESULTS: EMA has approved three classes of GLP-1 agonists for T2D and later for obesity: liraglutide (2009 and 2015), semaglutide (2018 and 2022) and tirzepatide (simultaneous approval in 2022). In Spain, all GLP-1s have been recommended for use within the National Health System for both indications within 2 years post EMA approval. However, France is yet to approve any of the three GLP-1 agonists for one or both indications. Regarding real-world off label use, Ozempic (semaglutide) is predominantly used off-label for weight loss; limited evidence exists for Victoza (liraglutide), while no evidence was found for Mounjaro (tirzepatide) as it was approved simultaneously for both indications.

CONCLUSIONS: Despite established efficacy of liraglutide and semaglutide in managing obesity through clinical trials and real-world off-label utilisation, obtaining approval for extended indications has been a prolonged process. This delay may have contributed to the existing challenge of intermittent supply and ongoing shortages of GLP-1 medications for patients with T2D.