Trulicity® (dulaglutide) and mood changes

What the Trulicity® documents say about mood

The US label’s warnings cover thyroid tumours, pancreatitis, low blood sugar with insulin or a sulfonylurea, allergic reactions, kidney injury, severe stomach reactions, diabetic eye disease, gallbladder disease and anaesthesia; none concerns mood. ^[1] The EU summary has no psychiatric entry in its table of adverse reactions. ^[3] The Canadian monograph, which lists every event seen in at least 1% during treatment, includes anxiety and insomnia with rates close to placebo. ^[4]

Mood appears in one place: the Medication Guide lists anxiety, irritability or mood changes among the signs of low blood sugar, next to shakiness, sweating, hunger and confusion. ^[2] The EU leaflet similarly includes irritability. ^[3]

The FDA’s 2026 review

In January 2026 the FDA asked for the suicidal behaviour and ideation warning to be removed from Saxenda®, Wegovy® and Zepbound®, the GLP-1 medicines approved for weight reduction. It noted that GLP-1 medicines approved for type 2 diabetes, such as Trulicity®, did not include such information, so the change brought all labels into line. ^[5]

The review pooled 91 placebo-controlled trials across GLP-1 drug programmes, with 60,338 people on a GLP-1 medicine and 47,572 on placebo, and found no increased risk of suicidal thoughts or behaviour, or of anxiety, depression, irritability or psychosis. ^[5] A separate FDA study of more than 2.2 million people with type 2 diabetes found no higher risk of intentional self-harm in those starting a GLP-1 medicine than in those starting an SGLT2 inhibitor. ^[5] The FDA still asks people to report new or worsening depression, suicidal thoughts or unusual changes in mood or behaviour to their health care professional. ^[5]

What other studies report for dulaglutide

A 2025 analysis of adverse event reports in the US, Canada and Australia found disproportionate reporting of depressive symptoms and suicidal ideation for semaglutide and of depression for liraglutide. For dulaglutide, the signals were for eating disorders and insomnia rather than depression. ^[6] A 2025 study across four international databases found no positive suicide signal for GLP-1 medicines as a class. ^[8] These analyses compare reporting patterns and cannot show cause. ^[6][8]

An Australian prescription study using a 10% sample of national dispensing records from 2012 to 2022 found that people dispensed exenatide, dulaglutide or semaglutide were more likely to be dispensed an antidepressant later, with a hazard ratio of 1.19. ^[7] The authors called for vigilance and more research. As an observational study it cannot show that the medicines caused the change, and depression is more common in people with long-term conditions such as diabetes. ^[7][9]

Why mood might shift on Trulicity®

• Low blood sugar: with insulin or a sulfonylurea, low readings were common, for example in about one in five people on a sulfonylurea over 78 weeks, and irritability, anxiety and mood changes are listed signs. ^[1][2]
• Poor sleep: insomnia was slightly more frequent on 1.5 mg than on placebo in Canadian data, and MedlinePlus lists sleeping too much or too little among the symptoms of depression. ^[4][9]
• Feeling unwell: nausea, fatigue and reduced appetite are the commonest Trulicity® reactions, especially in the first weeks. ^[1][3] MedlinePlus notes that some medical conditions and medicines cause symptoms that look like depression, and its list of depression symptoms includes tiredness and eating changes. ^[9]
• Living with diabetes: MedlinePlus notes that chronic conditions such as diabetes and heart disease often occur with depression and can make it worse. ^[9]

Other causes of mood changes

MedlinePlus describes depression as more than a few days of feeling sad or irritable: symptoms such as low mood or loss of interest that last most of the day, nearly every day, for at least two weeks. ^[9] It lists genetic, biological, environmental and psychological factors, hormonal changes, trauma and stressful life events among causes, and notes that thyroid disorders, viruses and some medicines can produce symptoms that look like depression. ^[9]

Symptoms vary with age and sex: children may seem irritable rather than sad, teenagers may act out or sleep excessively, and men may appear angry. ^[9] NIMH adds that depression is linked to heart disease and diabetes and is a risk factor for suicidal thoughts and behaviours. ^[10]

What the guidance describes

The FDA advises continuing your medicine as prescribed and discussing any concerns with your health care professional. ^[5] MedlinePlus says talking to your provider or a mental health professional is the first step if you think you might be depressed, and that getting help at the earliest sign can make symptoms easier to manage. ^[9] Treatment usually involves talk therapy, medicines or both. ^[9]

If you use insulin or a sulfonylurea, the label asks that you learn the signs of low blood sugar and how to treat them, so a sudden wave of irritability or anxiety can be checked against a glucose reading. ^[1][12]

Trulicity® is a registered trademark of Eli Lilly and Company. Saxenda® and Wegovy® 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 Eli Lilly and Company or Novo Nordisk.

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