A RECENT population-based analysis has highlighted potential behavioural side effects associated with Glucagon-like peptide 1 receptor agonists (GLP1RA). These medications, widely used for managing Type 2 diabetes and obesity, have gained popularity for their weight loss benefits.
GLP1RA medications mimic the GLP-1 hormone, which regulates insulin, blood glucose levels, and appetite, promoting feelings of fullness. This hormone binds to GLP-1 receptors (GLP1R) in the brain and pancreas, playing a crucial role in managing metabolic processes.
The study examined genetic variants in the GLP1R gene across diverse populations, including 408,774 white British individuals, 50,314 white Europeans, 7,667 South Asians, 10,437 individuals of multiple ancestries, and 7,641 African-Caribbeans.
Consistent associations between GLP1R variants and cardiometabolic traits, such as body mass index, blood pressure, and Type 2 diabetes, were observed across all ancestries. However, links between these genetic variants and behavioural traits, including risk-taking, mood instability, chronic pain, and anxiety, were less consistent and varied by ancestry.
Interestingly, the researchers identified that genetic variants influencing cardiometabolic traits were distinct from those affecting behavioural traits. Additionally, these genetic variations were separate from those influencing GLP1R gene expression levels.
The findings suggest that behavioural changes observed in individuals using GLP1RA are unlikely to result directly from the GLP1R pathway. This distinction may pave the way for a better understanding of the mechanisms behind such side effects and inform future research.
As GLP1RA medications continue to be hailed for their effectiveness in weight loss and diabetes management, these insights underline the importance of monitoring and addressing potential behavioural impacts. Further studies could explore the interplay between genetics, medication, and behaviour, ensuring a holistic approach to patient care.
The study underscores the need for personalised medicine approaches that consider genetic and behavioural factors to optimise the benefits of GLP1RA while minimising adverse effects.
Reference
Hayman MME et al. Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: a trans-ancestry study in UK Biobank. Diabetes Obes Metab. 2025;DOI:10.1111/dom.16178.
