Australia's Therapeutic Goods Administration (TGA) has issued a significant safety warning concerning GLP-1 receptor agonists, including popular medications like Ozempic (semaglutide) and Mounjaro (tirzepatide). These drugs, primarily intended for type two diabetes treatment but widely used for weight loss, have been linked to a higher risk of self-harming thoughts and behaviors.

On Monday, the TGA announced that a search of its Database of Adverse Event Notifications on September 23 uncovered 85 reports linking GLP-1 RAs to a decline in mental health. These reports included 72 instances of suicidal ideation, six cases of depressional suicide, four suicide attempts, two suicides, and one report of self-injurious ideation. The class of drugs under scrutiny includes Ozempic, Wegovy, Saxenda (liraglutide), Trulicity (dulaglutide), and Mounjaro.

This disturbing data prompted an investigation by an independent expert group, the Advisory Committee on Medicines. Previously, in June, the committee had reported insufficient evidence to establish a link between GLP-1 medications and suicidal ideation or behaviors. However, the new investigation, requested by the TGA, identified a 'complex interplay between mental illness and chronic endocrine disorders,' which GLP-1 RAs are used to treat. It also noted a 'potential relationship between weight loss and suicidal or self-harm ideation.'

The TGA's alert advises: 'Patients taking these medicines should tell their health professional if they experience new or worsening depression, suicidal thoughts or any unusual changes in mood or behaviour.' The Advisory Committee on Medicines also recommended 'harmonising' the information regarding GLP-1 RAs, stating that updates to packaging should convey a class-level awareness rather than implying a direct causal association. Consequently, the TGA has updated its advice for the entire class of medicines to include a warning about suicidal ideation.

In a separate but related development, the TGA has also updated its warning for Mounjaro (tirzepatide) following anecdotal reports of women becoming pregnant while on the drug. An investigation by the TGA concluded that a link between tirzepatide and the decreased effectiveness of oral contraception 'could not be ruled out.' A 2024 study suggested that tirzepatide doubled the time it took for ethinylestradiol (a synthetic estrogen in combined oral contraceptive pills) to be fully absorbed into the bloodstream. This delay might be due to tirzepatide's effect on slowing digestion, as ethinylestradiol is largely absorbed in the small intestine. However, five other studies found no change in ethinylestradiol levels in patients taking both oral contraceptives and tirzepatide.

As a result, the TGA will now advise Mounjaro patients to use non-oral contraception for the first four weeks of treatment and for four weeks following any dose increase. Furthermore, the TGA explicitly states: 'None of the GLP-1 RAs should be used during pregnancy, and individuals of childbearing potential are advised to use effective contraception during treatment with a GLP-1 RA.'

Novo Nordisk, the owner of Ozempic, affirmed its commitment to patient safety and transparency. Ana Svensson, their clinical, medical and regulatory vice-president, stated, 'Considering the totality of evidence from clinical trials, post-marketing reports and observational studies, Novo Nordisk believes that the benefit-risk profile of semaglutide remains favourable.' The company reiterated its dedication to maintaining up-to-date safety information and collaborating with health authorities globally.