OBJECTIVES: Glucagon-like peptide-1 (GLP-1) agonists reduce blood sugar and energy intake by activating the GLP-1 receptor and are used to manage type2 diabetes. GLP-1 agonists may also lead to weight loss and are garnering increased attention. Semaglutide, liraglutide and tirzepatide are approved for obesity treatment, while other GLP-1s are widely used off label. Despite the observed effectiveness of these medications for weight management, social media is rife with anecdotal narratives regarding a range of safety events. However, these adverse events are yet to be systematically assessed over time. This study aims to explore the criteria and requirements for a post authorisation safety study (PASS), review the current state of PASS for GLP-1s, and synthesize the potential path forward for assessing long-term safety of GLP-1s in the treatment of obesity.

METHODS: Desk research/targeted literature review of the use of GLP-1 in obesity, GLP-1 PASS, and the regulatory requirements for PASS.

RESULTS:

With regards to criteria for a PASS, medicines that signal adverse events that are; previously unknown, affect a particular group of patients or are associated with specific patient characteristic such age or weight or underlying conditions during pre-approval were most likely to be given a post marketing requirement.

To date, two out of the 29 PAS reported for GLP-1s were for obesity treatment; one was performed to assess in market use for liraglutide and another performed for a group of GLP-1 including liraglutide, semaglutide, dulaglutide, exenatide and lixisenatide to assess suicide and self-harm related events a scope too narrow compared to all potential adverse events.

CONCLUSIONS: GLP-1s have the potential to disrupt the healthcare ecosystem for the treatment of obesity however they have shown side effects that are not fully understood. As such PASS should be required for GLP-1s to fully evaluate their safety and measure effectiveness of risk management measures in this space.