Popular weight loss drugs (like Ozempic and Wegovy, otherwise known as Glucagon-like peptide 1 or GLP-1 agonists) are typically prescribed to people with diabetes, severe obesity and other serious obesity-related health conditions. However, GLP-1 agonists are now being used more widely for simple weight loss and are increasingly used globally, particularly by celebrities and internet influencers for rapid lifestyle weight loss, with limited clinical indications.

Professor Raymond Playford (UWL) and Professor Martin Deahl (Institute of Psychiatry, London) have observed anecdotally that the drugs may be causing patients to exhibit potentially reckless and "out of character" decision-making, including making major life-changing decisions regarding their domestic situation, such as divorce or moving house. The authors are recommending that research should be conducted to explore this risk and in the interim, patients starting GLP-1 agonists should be cautioned about making rapid life-changing decisions.

The authors of the article suggest that taking GLP-1 agonists may result in cognitive changes in decision-making through the combination of metabolic changes resulting from calorie deficit and rapid weight loss, in combination with the direct effects of the drug on brain function.

GLP-1 agonists increase brain dopamine levels, a brain-signaling chemical colloquially known as the "happy hormone" due to its role in feelings of happiness, pleasure and reward.

It is well-known that other drugs that influence dopamine levels in the brain (such as Levodopa, which is used in the treatment of Parkinson's Disease) impact decision-making and increase the risk of impulse control disorders. These side effects can include pathological gambling and hypersexuality, with the British National Formulary (used by medical professionals as a guide to dosage and side effect risk) advising that patients need to be warned about this risk. 

However, there is no equivalent advice for GLP-1 agonists in patient information leaflets or from government regulatory agencies. Current warnings about GLP-1 agonists mainly relate to gut motility issues, such as bloating, nausea and acid reflux.

The NICE (Semaglutide) website advises doctors to warn patients about potential impairment of driving and performance of skilled tasks. In the USA, FDA advice (Wegovy) also focuses on the potential development of psychosis and suicidal ideation, advising doctors to warn patients to be alert to sudden changes in mood, behaviours, thoughts or feelings.

However, effects on cognition (particularly decision-making abilities) have received little attention, with the very few studies that have been published focusing on longer-term outcomes, rather than during the early phase of starting treatment when rapid weight loss and dose escalation of GLP-1 therapy is taking place.

It is therefore imperative that as the indications for the use of these drugs expand, we remain vigilant for previously unrecognised side effects and keep patients informed about potential risks.

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