Australia’s TGA Updates Safety Warnings for GLP-1 Receptor Agonists and Tirzepatide: Suicidal Ideation Precautions and New Contraception Advice

On 1 December 2025, Australia’s Therapeutic Goods Administration (TGA) updated safety warnings for all GLP-1 receptor agonists (GLP-1 RAs) and the dual GIP/GLP-1 agonist tirzepatide. The warning was focused on two areas: a class-wide precaution about suicidal thoughts or behaviors, and revised contraception guidance specific to tirzepatide (Mounjaro). These updates follow TGA’s internal review, international regulatory assessments, advice from the Advisory Committee on Medicines (ACM), and analysis of Australia’s Database of Adverse Event Notifications (DAEN).

Suicidal Thoughts and Behaviors: Class-Wide Precaution

TGA aligned the Product Information (PI) and Consumer Medicine Information (CMI) for all marketed GLP-1 RAs in Australia, including Semaglutide (Ozempic, Wegovy), Liraglutide (Saxenda), dulaglutide (Trulicity) and tirzepatide (Mounjaro).

The new statement reads:

“Suicidal behavior and ideation have been reported with GLP-1 receptor agonists. Monitor patients for the emergence or worsening of depression, suicidal thoughts or behaviors, and any unusual changes in mood or behavior.”

DAEN reports up to September 2025 include 72 cases of suicidal ideation, 6 depression-related suicides, 4 suicide attempts, 2 completed suicides, and 1 case of self-injurious ideation among people using GLP-1 RAs in Australia. These reports do not prove causation. ACM concluded the current evidence is insufficient to support a causal link, but recommended harmonized warnings for consistent communication across the class.

International reviews by the EMA, FDA, MHRA and others have also found no disproportional or causal signal for suicidality in clinical trials or pharmacovigilance databases. Regulators continue surveillance, but current data support a precautionary approach rather than a confirmed risk.

Patients starting or continuing GLP-1 RA therapy should be monitored for mood changes, especially those with a history of depression or other psychiatric conditions.

Updated Contraception Advice for Tirzepatide (Mounjaro)

TGA issued new contraception guidance specific to tirzepatide (Mounjaro), following evidence that the medicine can delay gastric emptying, particularly after the first dose. This may reduce the effectiveness of oral contraceptives during initiation or after dose escalations.

TGA concluded that a reduced effectiveness of oral contraceptives could not be ruled out, and added the following precaution:

Patients using oral contraceptives should switch to a non-oral method or add a barrier method for 4 weeks after starting tirzepatide and for 4 weeks after each dose increase.

This advice reflects pharmacokinetic data showing the largest effect on gastric emptying early in treatment, with the impact diminishing over time.

Separately, GLP-1 RAs are not recommended during pregnancy, and individuals of childbearing potential are advised to use effective contraception throughout treatment. Clinicians also note that weight loss from GLP-1 RAs may improve fertility, which makes reliable contraception even more important.

Why the Changes Were Made

The updates follow:

• A TGA safety review incorporating DAEN data
• ACM consultation in June 2025
• International regulatory assessments
• Evidence on tirzepatide’s effects on gastric emptying
• The need to harmonize previously inconsistent PI/CMI statements across different GLP-1 products

TGA emphasizes that these updates do not change the approval status or availability of these medicines, but ensure clearer and more consistent risk communication.

What Healthcare Professionals Should Do

• Monitor all patients on GLP-1 RAs for mood or behavior changes.
• Evaluate the risk–benefit balance in individuals with pre-existing mental health conditions.
• For patients starting tirzepatide, advise on non-oral or barrier contraception during the 4-week precautionary window after initiation and each dose increase.
• Remind patients that GLP-1 RAs should be avoided in pregnancy and that reliable contraception is required during treatment.

Summary

TGA’s new harmonized warnings reflect a precautionary, evidence-based approach. While current data do not show a causal association between GLP-1 RAs and suicidality, consistent messaging across the class aims to support safe use as prescribing expands for diabetes and obesity. Tirzepatide now carries clear advice on contraception, acknowledging the potential for reduced oral contraceptive effectiveness early in treatment.