Popular weight-loss drug may influence risk-taking behavior

A large-scale genetic study has revealed an unexpected link between weight-loss drugs and behavioral changes, providing new insights into how these widely used drugs affect mental health and decision-making.

The study, published in the journal Diabetes, Obesity & Metabolism, examined genetic variations in nearly half a million people to understand how GLP-1 receptor drugs, which are currently making headlines for their weight-loss effects, affect physical and mental health.

Scientists analyzed data from UK Biobank, focusing on genetic variants targeted by popular drugs such as Wegovy and Ozempic. Their findings suggest that these genetic differences not only affect metabolism, but also traits such as risk-taking behavior and emotional stability—although importantly, these effects appear to work through different pathways than the drugs themselves.

The study was very broad, including more than 408,000 participants of British ancestry, as well as large numbers of participants of European, South Asian and African Caribbean ancestry. This diverse sample allows researchers to study how these genetic effects may differ in different populations.

Results differed significantly by ethnic background. Among white British and European participants, researchers found an association between genetic variants and risk-taking behavior. In other groups, the same genetic regions were associated with different mental health traits—including chronic pain in African-Caribbean participants and anxiety in multi-ancestry participants.

What is particularly interesting about these findings is that while genetic variants show consistent effects on metabolism across all racial groups, their effects on behavioral traits vary widely between populations. This shows that the relationship between these drugs and mental health may be more complex than previously thought.

The study also revealed some reassuring news for current users of these drugs. The study found no evidence that the drugs’ behavioral effects act directly through GLP-1 receptors, their primary target. This suggests that the effects of these drugs on mental health may be small or indirect.

The findings come at a critical time, as millions of people around the world are using or considering using these drugs to lose weight or manage diabetes. While the study does not show any immediate concerns about mental health risks, it highlights the importance of continued monitoring and research.

Investigations show that specific genetic variants associated with type 2 diabetes risk and blood pressure are consistent across racial groups. However, when it comes to behavioral traits, the effects are more diverse and complex, suggesting that individual responses to these drugs may vary depending on genetic background.

The team used sophisticated genetic analysis techniques to study how these variants affect gene expression in different body tissues. Their results show that while some genetic variants affect metabolism directly through the GLP-1 receptor, others influence behavior through entirely different mechanisms.

For health care providers and patients, these findings provide important context for discussing treatment options. While the study does not show any direct mental health risks from these drugs, it demonstrates the importance of individualized monitoring and consideration of individual patient factors when prescribing these drugs.

The study marks an important step toward understanding the broader effects of these increasingly popular drugs, while highlighting the need for continued research into their long-term effects on physical and mental health in diverse populations.