Wegovy® (injection) and mood changes

If you are in crisis

If you are having thoughts of suicide or of harming yourself, get help now: in the US call or text 988 (the 988 Suicide & Crisis Lifeline), or call your local emergency number wherever you are. ^[2] You do not need to decide first whether the medicine is involved.

What changed in January 2026

When Wegovy® was approved for weight management, its label included a warning about suicidal behaviour and ideation, a precaution carried over from older weight-loss medicines. In January 2026 the FDA asked the makers of Wegovy®, Saxenda® and Zepbound® to remove it. ^[2] The current Wegovy® prescribing information records the section as removed in 01/2026. ^[1]

The FDA’s review had three parts: a meta-analysis of 91 placebo-controlled trials covering 107,910 people, a claims-data study of more than two million people with type 2 diabetes comparing GLP-1 medicines with SGLT-2 inhibitors for intentional self-harm, and a review of published observational studies. None supported a causal link. ^[2] The agency still tells patients to report new or worsening depression, suicidal thoughts or unusual changes in mood or behaviour. ^[2]

What each official document says

What the STEP trials measured

A post hoc analysis pooled STEP 1, 2 and 3 (68 weeks, 3,377 adults) and STEP 5 (104 weeks). Depressive symptoms were measured with the PHQ-9 questionnaire and suicidal thoughts with a structured rating scale. Scores were low at the start and stayed low; people on semaglutide 2.4 mg were less likely than those on placebo to move into a more severe depression category, and 1% or fewer in either group reported suicidal thoughts or behaviour. Psychiatric adverse events were generally balanced. ^[6]

The limits matter. People with known major psychiatric illness were excluded, so the results describe people without it; the analysis was done after the trials ended; and several authors were Novo Nordisk employees. ^[6] The small improvement in depression scores was not considered clinically meaningful. ^[6]

Reports from outside trials

Spontaneous reports tell a different kind of story. An analysis of the EU EudraVigilance database from 2021 to May 2023 found that psychiatric events made up 1.2% of reports for semaglutide, liraglutide and tirzepatide combined; depression, anxiety and suicidal thoughts were the most frequent, and a small number of reports were serious. ^[7] Reports like these show what people noticed, but they cannot show that the medicine caused it, because nobody knows how many users had no problem.

In a large US health-records study of people with type 2 diabetes, semaglutide was not associated with a higher 12-month risk of depression, anxiety or suicidality than three other diabetes medicines. ^[8] That study was observational and used diabetes doses.

Why mood can shift during treatment

• In the label: if you have type 2 diabetes and also use insulin or a sulfonylurea, anxiety, irritability and mood changes can be signs of low blood sugar. ^[1] Tiredness was also more common on Wegovy® (11% vs 5% in adults), and fatigue can colour mood. ^[1]
• Proposed, not established: GLP-1 acts in parts of the brain that control appetite and food intake. ^[2] Post-marketing reports of psychiatric events led US and EU regulators to open investigations in July 2023, ^[2][3] but their reviews found no increased risk.
• General: MedlinePlus notes that depression has genetic, biological, environmental and psychological causes, is more common in women, often accompanies chronic conditions such as diabetes or heart disease, and that some medicines and illnesses can produce symptoms that look like depression. ^[9]

Other things that can affect mood

Stressful events, poor sleep and hormonal shifts around menstruation, pregnancy, the postpartum period and menopause can all bring on depressive symptoms. ^[9] Thyroid problems and viral illnesses are among the medical conditions that can mimic them. ^[9] A big change in eating habits, weight and routine can also stir up feelings that are worth talking through, whatever their cause.

MedlinePlus describes depression as more than a few days of sadness: symptoms most of the day, nearly every day, for at least two weeks, with low mood or loss of interest. ^[9] Changes that look like this deserve attention whether or not they started with Wegovy®.

Getting support

MedlinePlus says treatment usually involves talk therapy, medicines or both, that regular exercise, a consistent sleep schedule and stress control support mental health, and that seeing a provider at the earliest sign of a problem helps. ^[9] The FDA adds that people who disclose suicidal thoughts should be referred to mental health professionals. ^[2]

If you have a history of depression or have ever had suicidal thoughts, say so before starting Wegovy®; the Canadian patient information asks for exactly that. ^[5] If you already take an antidepressant, MedlinePlus advises against stopping it without first talking to your provider. ^[9]

Wegovy® and Saxenda® are registered trademarks of Novo Nordisk A/S. Zepbound® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Novo Nordisk or Eli Lilly and Company.