GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy) and liraglutide (Victoza, Saxenda) are widely prescribed for type 2 diabetes and obesity management. Recent concerns have emerged regarding a potential link between GLP-1 agonists and suicidal ideation, prompting regulatory reviews by the MHRA and EMA. Current evidence from large-scale clinical trials does not establish a causal relationship, though post-marketing reports continue to be monitored. This article examines the available evidence, regulatory guidance, and practical advice for patients and healthcare professionals regarding mental health considerations when using these medications.

What Are GLP-1 Agonists and How Do They Work?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily used to manage type 2 diabetes mellitus and, more recently, obesity. These medicines include semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), and dulaglutide (Trulicity). Exenatide (Byetta, Bydureon) is less commonly used in the UK as these products have been largely withdrawn from the market. Semaglutide is available as both injectable (Ozempic, Wegovy) and oral (Rybelsus) formulations.

The mechanism of action involves several complementary effects. GLP-1 agonists stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner, meaning they promote insulin release only when blood glucose levels are elevated. This reduces the risk of hypoglycaemia when used alone, though this risk increases when combined with insulin or sulfonylureas. Simultaneously, they suppress glucagon secretion, a hormone that raises blood glucose levels. These medications also slow gastric emptying, which helps to reduce post-meal glucose spikes and promotes satiety.

The appetite-suppressing effects occur through actions on the central nervous system, particularly in areas of the brain that regulate hunger and food intake. This has led to their licensed use for weight management in individuals with obesity or those who are overweight with weight-related comorbidities. GLP-1 agonists are typically administered via subcutaneous injection, either daily or weekly depending on the specific formulation, with the exception of oral semaglutide.

Some of these medications have demonstrated significant benefits in cardiovascular risk reduction in people with type 2 diabetes, with specific agents (including liraglutide, semaglutide and dulaglutide) showing reductions in major adverse cardiovascular events. However, like all medications, they carry potential adverse effects that require careful monitoring and patient education.

Understanding the Link Between GLP-1 Agonists and Suicidal Ideation

Concerns regarding a potential association between GLP-1 receptor agonists and suicidal ideation emerged following post-marketing surveillance reports and patient accounts. Suicidal ideation refers to thoughts about or preoccupation with suicide, ranging from fleeting considerations to detailed planning. It represents a serious psychiatric symptom requiring immediate clinical attention.

The proposed link between these medications and mental health effects remains controversial and not definitively established. Some patients and healthcare professionals have reported new or worsening depression, anxiety, or suicidal thoughts following initiation of GLP-1 agonist therapy. However, establishing causality is complex, as multiple confounding factors exist. Individuals with obesity and type 2 diabetes have higher baseline rates of depression and mental health conditions compared with the general population, making it difficult to determine whether reported symptoms represent medication effects or underlying psychiatric comorbidity.

Several theoretical mechanisms have been proposed, though none are conclusively proven. GLP-1 receptors are present in various brain regions involved in mood regulation, including the hippocampus and prefrontal cortex. It is theoretically possible that pharmacological manipulation of these receptors could influence mood and behaviour. Additionally, rapid weight loss itself—regardless of the method—has been associated with mood changes in some individuals, potentially due to hormonal shifts, nutritional factors, or psychological adjustment challenges.

Some researchers have suggested that GLP-1 agonists might have potential neuroprotective effects and could theoretically improve mood in certain contexts, though this is based primarily on preclinical studies and limited human data. The relationship between these medications and mental health appears complex and likely varies between individuals based on genetic factors, pre-existing psychiatric conditions, and other medications. It is worth noting that many clinical trials of GLP-1 agonists excluded people with significant psychiatric illness, which may limit our understanding of effects in these populations.

Current Evidence and Regulatory Guidance from MHRA and EMA

Regulatory authorities including the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK and the European Medicines Agency (EMA) have carefully reviewed available evidence regarding GLP-1 agonists and mental health concerns. As of current guidance, there is no established causal relationship between these medications and suicidal ideation or self-harm based on clinical trial data and pharmacovigilance reviews.

Large-scale randomised controlled trials of GLP-1 agonists, including cardiovascular outcome studies involving tens of thousands of participants, have not demonstrated an increased risk of suicidal ideation or behaviour compared with placebo. The EMA's Pharmacovigilance Risk Assessment Committee (PRAC) conducted a comprehensive safety review in 2023–2024 examining reports of suicidal and self-injurious thoughts with GLP-1 receptor agonists used for both diabetes and weight management. Their assessment concluded that available evidence does not support a causal association between these medicines and suicidal ideation.

However, regulatory bodies maintain ongoing surveillance of post-marketing reports and continue to monitor the safety profile of these medications. The MHRA encourages healthcare professionals and patients to report any suspected adverse reactions through the Yellow Card scheme (yellowcard.mhra.gov.uk or via the Yellow Card app), which is essential for detecting rare or previously unrecognised safety signals.

It is important to note that UK product information for weight management GLP-1 agonists (Wegovy and Saxenda) does include warnings to monitor patients for depression or suicidal thoughts, despite no established causal link. For example, the Wegovy Summary of Product Characteristics advises healthcare professionals to monitor patients for depression, suicidal thoughts or suicidal behaviour, and to discontinue treatment if these occur. The National Institute for Health and Care Excellence (NICE) guidelines for diabetes and obesity management recommend individualised assessment when prescribing these medications, with NHS access to weight management formulations following specific NICE criteria (TA875).

Patients should be reassured that regulatory authorities continue to prioritise medication safety whilst recognising the substantial benefits these medicines offer for metabolic health.

Recognising Warning Signs and When to Seek Medical Help

Whilst there is no official causal link established between GLP-1 agonists and suicidal ideation, patients and carers should remain vigilant for any changes in mood or mental wellbeing when starting or adjusting these medications. Early recognition of warning signs enables timely intervention and support.

Key warning signs that warrant medical attention include:

• Persistent low mood or sadness lasting more than two weeks

• Loss of interest in previously enjoyed activities

• Changes in sleep patterns—either insomnia or excessive sleeping

• Significant anxiety or agitation that interferes with daily functioning

• Thoughts of self-harm or suicide, even if fleeting

• Feelings of hopelessness or worthlessness

• Social withdrawal from family and friends

• Difficulty concentrating or making decisions

Immediate action is required if you or someone you know experiences active suicidal thoughts, plans for self-harm, or believes they might act on suicidal ideation. In such circumstances:

• Contact emergency services (999) or attend the nearest Accident & Emergency department

• Call NHS 111 for urgent but non-life-threatening concerns

• Contact your local NHS urgent mental health helpline (search online for 'NHS urgent mental health helpline' and your location)

• Call the Samaritans (116 123, available 24/7) for immediate emotional support

• Do not leave the person alone if they are at immediate risk

For non-emergency concerns about mood changes whilst taking GLP-1 agonists, patients should contact their GP or diabetes specialist nurse within 24–48 hours. If suicidal thoughts emerge, seek urgent medical advice as clinicians may recommend stopping the medication. For other concerns, it is important not to stop the medication abruptly without medical advice, as this could affect diabetes control or weight management. Healthcare professionals can assess whether symptoms are medication-related, require psychiatric referral, or reflect other underlying conditions requiring treatment.

Family members and carers play a vital role in monitoring for subtle changes that patients themselves may not recognise, particularly in the early weeks of treatment.

Safe Use of GLP-1 Agonists: What Patients Should Know

Safe and effective use of GLP-1 receptor agonists requires partnership between patients and healthcare professionals, with attention to both physical and mental wellbeing throughout treatment.

Before starting treatment, patients should:

• Disclose their complete medical history, including any current or previous mental health conditions such as depression, anxiety, bipolar disorder, or previous suicidal ideation

• List all current medications; while significant pharmacokinetic interactions with psychiatric medications are not generally expected, GLP-1 agonists may affect absorption of some oral medications due to delayed gastric emptying

• Discuss realistic expectations regarding weight loss and diabetes control to avoid disappointment that might affect mood

• Ensure adequate support systems are in place, including regular contact with healthcare providers

• Discuss pregnancy plans as these medications are not recommended during pregnancy or breastfeeding; semaglutide should be discontinued at least two months before a planned pregnancy

During treatment, patients should:

• Attend all scheduled follow-up appointments to monitor both metabolic parameters and general wellbeing

• Keep a symptom diary noting any mood changes, particularly in the first three months of treatment

• Maintain open communication with healthcare providers about any concerns, however minor they may seem

• Continue existing mental health treatments unless specifically advised otherwise by a psychiatrist

• Adopt healthy lifestyle measures including regular physical activity, adequate sleep, and balanced nutrition, which support both metabolic and mental health

• Be aware that hypoglycaemia risk increases when GLP-1 agonists are used with insulin or sulfonylureas, and dose adjustments of these medications may be needed

Common adverse effects of GLP-1 agonists include nausea, vomiting, diarrhoea, and constipation, which typically improve over time. These gastrointestinal symptoms can affect quality of life and potentially mood, so managing them effectively with dietary adjustments and anti-emetics when necessary is important.

Seek immediate medical attention for serious adverse effects including:

• Severe, persistent abdominal pain (possible pancreatitis)

• Symptoms of gallstones (pain in upper right abdomen, especially after eating)

• Signs of dehydration or acute kidney injury (reduced urination, dizziness)

• Persistent severe constipation or abdominal distension (possible ileus)

• New or worsening vision problems (potential diabetic retinopathy complications)

Patients should understand that discontinuation may be appropriate if significant mental health concerns arise, even in the absence of proven causality. The decision to continue or stop treatment should be made collaboratively, weighing the metabolic benefits against any potential risks to psychological wellbeing. Alternative diabetes or weight management strategies can be explored if GLP-1 agonists are not suitable for an individual patient.

Report any suspected side effects to the MHRA through the Yellow Card scheme at yellowcard.mhra.gov.uk or via the Yellow Card app.

Frequently Asked Questions