Product information across the GLP-1 RA class has been updated to warn of potential risk of suicidal ideation and behaviour, the TGA announced on Monday.

The Advisory Committee on Medicines provided independent advice as part of a comprehensive investigation, ultimately concluding that “the evidence available was not sufficient to support an association between GLP-1 RAs and suicidal or self-injurious ideation,” the TGA explained in a Medicine Safety Update on Monday.

The TGA said a search of its Database of Adverse Event Notifications on 23 September 2025 for the GLP-1 RA class (semaglutide, liraglutide, dulaglutide and tirzepatide) found:

• 72 reports for suicidal ideation
• 6 reports for depressional suicide
• 4 reports of suicide attempt
• 2 reports of completed suicide
• 1 report of self-injurious ideation.

“While finding insufficient evidence for causality, the ACM noted there was a complex interplay between mental illness and chronic endocrine disorders for which GLP-1 RAs may be used for treatment, and the potential relationship between weight loss and suicidal/self-injurious ideation,” the TGA said.

It said the changes were made to ensure consistent information regarding the potential risk of suicidal thoughts or behaviours.

The following wording has been added to the PIs of GLP-1 receptor agonists (except Saxenda as it already included suitable wording):

Psychiatric disorders

Suicidal behaviour and ideation have been reported with GLP-1 receptor agonists. Monitor patients for the emergence or worsening of depression, suicidal thoughts or behaviours, and/or any unusual changes in mood or behaviour. Consider the benefits and risks for individual patients prior to initiating or continuing therapy in patients with suicidal thoughts or behaviours or have a history of suicidal attempts.

Like the TGA, the US Food and Drug Administration (FDA), Health Canada and the UK’s Medicine &  Healthcare products Regulatory Agency all say that their own reviews have not found evidence of a causal association between the drugs and suicidal ideation or suicide, but are continuing to monitor the risk.

The FDA’s November 2024 update said that detailed reviews of its Adverse Event Reporting System and clinical trials did not find an association, but “because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, we cannot definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue.”

WHO guideline issues conditional recommendation for GLP-1s as long-term obesity treatment

The updated PI wording comes as The World Health Organisation released global guidelines which conditionally recommend GLP-2 RAs and GIP/GLP-1 dual agonists for the long term treatment of obesity in adults (but not pregnant women), based on moderate certainty evidence.

“While the efficacy of these therapies in treating obesity and improving metabolic and other outcomes was evident, the recommendation is conditional due to limited data on their long-term efficacy and safety, maintenance and discontinuation, their current costs, inadequate health-system preparedness, and potential equity implications,” the WHO said in an accompanying statement.

“Currently, the accessibility, affordability and availability of GLP-1 receptor agonists and GIP/GLP-1 dual agonists remain highly inadequate to meet the population-level needs,” the WHO guideline stated.

The WHO also issued another conditional recommendation, that intensive behavioural therapy, including structured interventions involving healthy diet and physical activity, may be provided as a co-intervention alongside GLP-1s. This was based on low-certainty evidence that it might improve outcomes.

Interplay of weight and mental health

The Royal Australian and New Zealand College of Psychiatrists (RANZCP) said it acknowledged the TGA’s warning regarding potential mental health risks, “while also recognising the World Health Organisation’s  guidelines recommending these medications as long-term treatments for obesity.”

“GLP-1 RAs represent an important breakthrough in obesity treatment, including for people who often struggle with weight management due to their mental health conditions or their medications used to treat them,” the RANZCP stated, adding that it concurred with the TGA’s advice for health professionals to monitor for mental health effects in those taking the medications.

“Clinicians should carefully weigh the benefits and risks of initiating or continuing therapy, particularly in patients with suicidal thoughts or behaviours or who have a history of suicide attempts,” RANZCP said.

“In every case, clinicians should be aware of the full range of treatment options available and be informed by the evidence base when prescribing.”

The TGA said health professionals should:

• monitor patients taking GLP-1s for new onset or worsening of depression, suicidal thoughts or behaviours or an or any unusual changes in mood or behaviour
• advise patients to let their health professional know if they experience any of these
• consider the benefits and risks for individual patients before initiating or continuing therapy in patients with suicidal thoughts or behaviours.