Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide and liraglutide, are licensed for managing type 2 diabetes and weight-related conditions. Whilst these medications work primarily by regulating blood glucose and appetite, emerging interest surrounds their potential effects on mental health. GLP-1 receptors exist in brain regions involved in mood regulation, prompting questions about whether these medicines might influence anxiety. However, GLP-1 medications are not licensed or recommended for treating anxiety disorders. This article examines the current evidence, explores possible mechanisms linking metabolic and mental health, and provides guidance on discussing anxiety concerns with your GP if you are considering or taking GLP-1 treatment.

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

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily licensed for the management of type 2 diabetes mellitus and, more recently, for weight management in adults with obesity or overweight with weight-related comorbidities. These medicines include semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide (Byetta, Bydureon).

GLP-1 is a naturally occurring incretin hormone released by the intestines in response to food intake. GLP-1 receptor agonists work by mimicking this endogenous hormone, binding to GLP-1 receptors found throughout the body. Their primary mechanisms of action include:

• Enhancing insulin secretion from pancreatic beta cells in a glucose-dependent manner, which helps lower blood glucose levels without causing hypoglycaemia when used alone

• Suppressing glucagon release from pancreatic alpha cells, reducing hepatic glucose production

• Slowing gastric emptying, which prolongs satiety and reduces appetite

• Acting on appetite centres in the brain, particularly the hypothalamus, to reduce food intake

Most GLP-1 receptor agonists are administered via subcutaneous injection, with dosing frequencies ranging from twice daily to once weekly depending on the specific formulation. Oral semaglutide (Rybelsus) is also available in the UK. These medicines are licensed for different indications – some specifically for type 2 diabetes (e.g., Ozempic, Trulicity), while others are licensed for weight management (e.g., Wegovy, Saxenda) in line with NICE guidance.

Whilst GLP-1 receptors are abundant in the pancreas and gastrointestinal tract, they are also present in various brain regions, including areas involved in mood regulation and emotional processing. This widespread distribution has prompted research into potential effects beyond metabolic control, including impacts on mental health and anxiety.

The Link Between GLP-1 Agonists and Mental Health

The relationship between GLP-1 medications and mental health, particularly anxiety, is an emerging area of clinical interest. There is currently no official established link between GLP-1 receptor agonists and anxiety reduction, and these medications are not licensed or recommended for treating anxiety disorders. However, several biological mechanisms and clinical observations warrant consideration.

GLP-1 receptors are expressed in brain regions associated with emotional regulation, including the hippocampus, amygdala, and prefrontal cortex. Animal studies have suggested that GLP-1 signalling may influence neuroplasticity, neuroinflammation, and stress responses, though translating these findings to human anxiety disorders remains speculative.

The connection between metabolic health and mental wellbeing is well documented. People with type 2 diabetes and obesity experience higher rates of depression and anxiety compared to the general population. This relationship is bidirectional and complex, involving:

• Inflammatory pathways that affect both metabolic and mental health

• Hormonal dysregulation impacting mood and stress responses

• Psychosocial factors including stigma, body image concerns, and chronic disease burden

• Lifestyle factors such as reduced physical activity and poor sleep quality

When GLP-1 medications improve glycaemic control, facilitate weight loss, and enhance overall metabolic health, patients may experience secondary improvements in psychological wellbeing. This could manifest as reduced anxiety symptoms, though such effects would likely be indirect rather than a direct pharmacological action on anxiety pathways.

It is important to note that regulatory bodies including the MHRA and EMA continue to monitor the safety profile of GLP-1 receptor agonists, including any potential psychiatric effects. Recent reviews by these agencies have found no evidence of a causal association between GLP-1 receptor agonists and suicidal thoughts or self-harm, though vigilance continues. Current evidence does not support using these medications specifically for anxiety management outside their licensed indications.

Potential Mental Health Effects of GLP-1 Treatment

Clinical experience and emerging research suggest that GLP-1 receptor agonists may influence mental health in various ways, though the evidence base remains limited and findings are mixed. Understanding both potential benefits and risks is essential for informed clinical decision-making.

Possible positive effects that some patients report include:

• Improved mood and reduced anxiety symptoms potentially linked to successful weight loss and better metabolic control

• Enhanced self-esteem and body image as weight reduction progresses

• Reduced food-related anxiety and preoccupation with eating, though evidence for effects on binge eating is limited and observational

• Better sleep quality in some patients, though this is anecdotal and not well-established in clinical trials

These improvements, when they occur, are generally considered secondary to metabolic benefits rather than direct anxiolytic effects. The psychological impact of achieving health goals and regaining a sense of control over one's health should not be underestimated.

However, potential adverse mental health effects have also been reported and require vigilance:

• Nausea and gastrointestinal symptoms, common side effects of GLP-1 medications, may increase anxiety in susceptible individuals

• Rapid weight loss can occasionally trigger psychological distress or exacerbate eating disorder behaviours

• Mood changes, including low mood, have been reported in post-marketing surveillance, though causality remains uncertain

• Some patients report feeling emotionally flat or detached, though this is anecdotal and not well characterised in clinical trials

The Summary of Product Characteristics (SmPC) for GLP-1 receptor agonists used for weight management (such as Saxenda and Wegovy) includes specific warnings about monitoring for mood disorders and suicidal thoughts. If you experience new or worsening anxiety, low mood, or suicidal thoughts whilst taking a GLP-1 medication, seek urgent help immediately. Call 999 or go to A&E if you feel unsafe, contact NHS 111 for urgent advice, or call the Samaritans on 116 123 for immediate support. Also inform your GP as soon as possible. Do not stop the medication without medical advice, as abrupt discontinuation may affect your diabetes or weight management.

Patients with pre-existing mental health conditions, including anxiety disorders, should not be automatically excluded from GLP-1 treatment, but may benefit from closer monitoring and coordinated care between their GP, diabetes specialist, and mental health professionals. Those with active eating disorders should be assessed and managed according to NICE guidance before initiating or continuing weight-loss treatments.

If you experience any suspected side effects, report them to the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk.

What to Discuss with Your GP About GLP-1 and Anxiety

If you are considering GLP-1 treatment or are currently taking these medications and have concerns about anxiety, an open conversation with your GP is essential. Being prepared for this discussion will help ensure your treatment plan addresses both your metabolic and mental health needs.

Before starting GLP-1 treatment, inform your GP about:

• Current or previous anxiety disorders, including generalised anxiety disorder, panic disorder, social anxiety, or health anxiety

• Other mental health conditions such as depression, eating disorders, or obsessive-compulsive disorder

• Current psychiatric medications, as weight loss may affect medication requirements though GLP-1 medications themselves have few direct drug interactions

• Previous experiences with weight loss or diabetes medications and any associated mood changes

• Your support network and coping strategies for managing stress and anxiety

Your GP can help establish baseline mental health status and develop a monitoring plan. This might include validated questionnaires such as the GAD-7 (Generalised Anxiety Disorder-7) to track anxiety symptoms over time.

During GLP-1 treatment, maintain regular contact with your healthcare team and report:

• Any new or worsening anxiety symptoms, including excessive worry, panic attacks, or physical anxiety symptoms

• Changes in mood, sleep patterns, or appetite beyond expected treatment effects

• Difficulty coping with side effects such as nausea, which may exacerbate anxiety

• Concerns about body image or eating behaviours as weight changes occur

NICE guidance recommends holistic care for people with diabetes and obesity, recognising the importance of psychological wellbeing. Your GP may:

• Refer you to psychological services if anxiety symptoms are significant, including NHS Talking Therapies for anxiety and depression

• Consider whether anxiety treatment should be optimised before or alongside GLP-1 therapy, following NICE guidance for anxiety disorders

• Coordinate care with diabetes specialists, dietitians, and mental health professionals

• Review the risk-benefit balance of continuing GLP-1 treatment if mental health concerns arise

• Screen for and manage eating disorders according to NICE guidance before initiating or continuing weight-loss treatments

Remember that GLP-1 medications are not a treatment for anxiety, and any mental health benefits are likely secondary to metabolic improvements. If anxiety is a primary concern, evidence-based treatments such as cognitive behavioural therapy (CBT) and, where appropriate, anxiolytic medications remain the gold standard. Your GP can help integrate metabolic and mental health care to optimise your overall wellbeing.

Frequently Asked Questions