Rybelsus (semaglutide) is an oral GLP-1 receptor agonist licensed in the UK for treating type 2 diabetes mellitus in adults. Whilst this medication effectively improves blood glucose control, some patients have reported experiencing mood changes during treatment. Understanding the potential mental health side effects of Rybelsus is important for both patients and healthcare professionals. This article examines the current evidence regarding Rybelsus and mental wellbeing, explores how to recognise mood changes, and provides guidance on managing concerns and knowing when to seek medical advice. It's essential to note that regulatory reviews have found no established causal link between semaglutide and psychiatric side effects.

What Is Rybelsus and How Does It Work?

Rybelsus (semaglutide) is an oral medication licensed in the UK for the treatment of type 2 diabetes mellitus in adults. It belongs to a class of medicines called glucagon-like peptide-1 (GLP-1) receptor agonists, which work by mimicking the action of a naturally occurring hormone that helps regulate blood sugar levels.

The mechanism of action involves several key processes. Semaglutide stimulates insulin secretion from the pancreas when blood glucose levels are elevated, whilst simultaneously suppressing the release of glucagon, a hormone that raises blood sugar. Additionally, it slows gastric emptying, which helps reduce post-meal glucose spikes and promotes a feeling of fullness. These combined effects contribute to improved glycaemic control and often result in weight loss.

Rybelsus is prescribed as an adjunct to diet and exercise when these alone are insufficient to control blood sugar. It may be used as monotherapy when metformin is inappropriate (contraindicated or not tolerated), or in combination with other diabetes medications. The tablets must be taken once daily in the morning on an empty stomach with up to 120 ml of water only. The tablet should be swallowed whole, and you must wait at least 30 minutes before consuming any food, drink or other oral medicines to ensure optimal absorption.

NICE guidance (NG28) supports the use of GLP-1 receptor agonists in specific circumstances for type 2 diabetes management, particularly when weight management would be beneficial alongside glycaemic control. It's important to note that Rybelsus is not licensed for weight management in the UK.

Whilst Rybelsus is generally well-tolerated, like all medications it can cause side effects. The most commonly reported adverse effects are gastrointestinal, including nausea, vomiting, diarrhoea, and abdominal discomfort. Serious side effects can include pancreatitis, gallbladder disease and diabetic retinopathy complications. Patients and healthcare professionals have increasingly raised questions about potential effects on mental health and mood, prompting closer examination of this aspect of the drug's safety profile.

Recognising Mood Changes While Taking Rybelsus

Understanding the relationship between Rybelsus and mental health requires careful consideration of available evidence. Currently, there is no official established link between semaglutide and specific psychiatric side effects in the product's Summary of Product Characteristics (SmPC) approved by the MHRA. A 2024 review by the European Medicines Agency (EMA) and MHRA concluded that available evidence does not support a causal association between GLP-1 receptor agonists (including semaglutide) and suicidal thoughts or behaviour.

Nevertheless, some patients taking Rybelsus have reported experiencing mood changes, including:

• Low mood or feelings of depression

• Increased anxiety or nervousness

• Irritability or mood swings

• Changes in sleep patterns

• Reduced motivation or interest in activities

It is important to recognise that establishing causation is complex. Type 2 diabetes itself is associated with higher rates of depression and anxiety, with research suggesting that individuals with diabetes are around twice as likely to experience depression compared to the general population. The burden of managing a chronic condition, concerns about complications, and the physiological effects of fluctuating blood glucose levels can all impact mental wellbeing.

Additionally, the gastrointestinal side effects commonly experienced with Rybelsus—particularly persistent nausea—can indirectly affect mood and quality of life. Weight changes may also influence psychological wellbeing in some individuals.

If you notice mood changes after starting Rybelsus, it is worth keeping a symptom diary noting when changes occur, their severity, and any potential triggers. Check whether symptoms coincide with high or low blood glucose levels, as these can affect mood. This information can be invaluable when discussing your concerns with your GP or diabetes specialist nurse. Remember that correlation does not necessarily mean causation, and a thorough assessment is needed to determine the underlying cause of any mood disturbances.

Managing Mental Health Concerns on Rybelsus

If you are experiencing mood changes whilst taking Rybelsus, several practical strategies may help whilst you seek professional guidance. Do not stop taking your medication abruptly without consulting your healthcare team, as this could affect your diabetes control.

Optimising diabetes management itself can positively impact mental health. Maintaining stable blood glucose levels through regular monitoring, adhering to dietary recommendations, and engaging in physical activity can help reduce mood fluctuations. Structured education programmes such as DESMOND or X-PERT Health can provide valuable support for managing type 2 diabetes effectively.

Addressing gastrointestinal side effects may indirectly improve wellbeing. These symptoms often diminish over time as your body adjusts to the medication. Eating smaller, more frequent meals, avoiding high-fat foods, and staying well-hydrated can help manage nausea. Your prescriber may consider slower dose titration or temporary dose adjustments to minimise discomfort. If you're unable to keep fluids down, seek medical advice promptly.

If you take Rybelsus alongside insulin or sulfonylureas, discuss dose adjustments with your healthcare team to reduce the risk of hypoglycaemia, which can affect mood.

Psychological support is an important component of diabetes care. NICE recommends that healthcare professionals should be alert to depression and anxiety in people with diabetes and offer appropriate support. This might include:

• Talking therapies such as cognitive behavioural therapy (CBT)

• Diabetes-specific psychological interventions

• Peer support groups for people with diabetes

• Referral to mental health services if symptoms are moderate to severe

Many areas have NHS Talking Therapies services (formerly IAPT) in England that can be accessed through self-referral or GP referral. Scotland, Wales and Northern Ireland have different access routes to psychological support. Additionally, organisations such as Diabetes UK provide helplines and online communities where you can connect with others managing similar challenges.

Lifestyle factors including regular exercise, adequate sleep, stress management techniques, and maintaining social connections all contribute to mental wellbeing and should be prioritised alongside medical treatment.

When to Seek Medical Advice About Rybelsus Side Effects

Knowing when to contact your healthcare team is crucial for safe medication management. You should contact your GP or diabetes specialist nurse if you experience:

• Persistent low mood lasting more than two weeks

• Significant anxiety that interferes with daily activities

• Loss of interest in activities you previously enjoyed

• Changes in sleep or appetite beyond those explained by gastrointestinal side effects

• Difficulty concentrating or making decisions

• Feelings of hopelessness or worthlessness

Seek urgent medical attention by contacting your GP, calling NHS 111, or attending A&E if you experience:

• Thoughts of self-harm or suicide

• Severe depression that prevents you from functioning

• Panic attacks or severe anxiety episodes

• Any mental health crisis

Call 999 or go to A&E immediately if you are at immediate risk of harm.

For immediate support with suicidal thoughts, contact the Samaritans on 116 123 (available 24/7) or text SHOUT to 85258 for the crisis text service.

You should also seek urgent medical advice for physical symptoms that could indicate serious side effects of Rybelsus, including:

• Severe, persistent upper abdominal pain (with or without vomiting) which could indicate pancreatitis

• Symptoms of gallbladder disease such as pain in the upper right abdomen, fever or yellowing of the skin/eyes

• Inability to keep fluids down or signs of dehydration

• Sudden changes in vision, which could relate to diabetic retinopathy complications

When discussing concerns with your healthcare provider, be prepared to provide information about:

• When symptoms started in relation to beginning Rybelsus

• Severity and frequency of mood changes

• Impact on daily functioning and quality of life

• Any previous history of mental health conditions

• Other medications you are taking

• Recent life stressors or changes

Your healthcare team can conduct a thorough assessment to determine whether symptoms are related to Rybelsus, your diabetes, other factors, or a combination. They may consider adjusting your diabetes medication, providing additional support for mental health, or referring you to specialist services. The MHRA Yellow Card scheme (yellowcard.mhra.gov.uk) allows patients and healthcare professionals to report suspected side effects, contributing to ongoing medication safety monitoring. Remember that your mental health is as important as your physical health, and seeking help is a sign of strength, not weakness.

Frequently Asked Questions