Rybelsus (semaglutide) is an oral GLP-1 receptor agonist licensed in the UK for treating type 2 diabetes mellitus in adults. Whilst gastrointestinal side effects such as nausea and vomiting are well documented, some patients report experiencing mood swings or irritability whilst taking this medication. However, mood changes are not officially recognised as a side effect in the MHRA-approved product literature. This article examines the potential link between Rybelsus and mood fluctuations, explores possible contributing factors such as hypoglycaemia and gastrointestinal discomfort, and provides practical guidance on managing symptoms and when to seek medical advice.

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 is indicated as an adjunct to diet and exercise, either as monotherapy when metformin is inappropriate or as an add-on to other diabetes medications. It belongs to a class of medicines called glucagon-like peptide-1 (GLP-1) receptor agonists. Rybelsus is the first GLP-1 receptor agonist available in tablet form, offering an alternative to injectable formulations for patients who prefer oral administration.

The active ingredient, semaglutide, works by mimicking the action of a naturally occurring hormone called GLP-1. This hormone is released by the intestines in response to food intake and plays several important roles in glucose regulation. Semaglutide stimulates insulin secretion from the pancreas when blood glucose levels are elevated, helping to lower blood sugar after meals. It also suppresses the release of glucagon, a hormone that raises blood glucose, and slows gastric emptying, which reduces the rate at which glucose enters the bloodstream.

Additionally, semaglutide acts on receptors in the brain that regulate appetite, often leading to reduced food intake and weight loss. While weight reduction may occur, it's important to note that Rybelsus is not licensed for weight management in the UK.

Rybelsus is initiated at 3 mg once daily for 30 days, then increased to 7 mg once daily. After at least 30 days on the 7 mg dose, it can be increased to 14 mg once daily if needed for better glycaemic control. The medication must be taken with up to 120 ml of water, swallowed whole (not split or crushed), on an empty stomach, at least 30 minutes before the first food, drink, or other oral medicines of the day. If a dose is missed, the patient should skip that dose and take the next scheduled dose the following day.

Rybelsus may affect the absorption of other oral medicines, and patients taking levothyroxine should have their thyroid function monitored when starting treatment. According to NICE guidance (NG28), GLP-1 receptor agonists like Rybelsus are recommended as part of a comprehensive treatment plan that includes diet, exercise, and other glucose-lowering therapies when appropriate.

Common Side Effects of Rybelsus in the UK

Like all medications, Rybelsus can cause side effects, although not everyone experiences them. The most frequently reported adverse effects are gastrointestinal in nature, particularly during the initial weeks of treatment or following dose increases. These include:

• Nausea (very common, affecting more than 1 in 10 people)

• Vomiting and diarrhoea (common)

• Abdominal pain and decreased appetite (common)

• Constipation, indigestion, and flatulence (common)

These gastrointestinal symptoms typically diminish over time as the body adjusts to the medication. Taking Rybelsus exactly as prescribed and eating smaller, more frequent meals may help reduce these effects.

Other common side effects include dizziness, fatigue, and headache. Hypoglycaemia (low blood sugar) is uncommon when Rybelsus is used alone but more likely when combined with sulphonylureas or insulin. Signs of hypoglycaemia include trembling, sweating, confusion, palpitations, and hunger.

Patients should be aware of potential complications including gallbladder disease (symptoms include right upper abdominal pain, fever, or jaundice) and the risk of dehydration leading to acute kidney injury with persistent gastrointestinal symptoms. In people with pre-existing diabetic retinopathy, there is a risk of worsening, particularly when starting treatment, and appropriate monitoring is advised.

Regarding mood changes or mood swings, there is no official established link between Rybelsus and direct psychiatric effects in the product literature approved by the MHRA (Medicines and Healthcare products Regulatory Agency). However, some patients have anecdotally reported feeling irritable, anxious, or experiencing mood fluctuations. These reports may be related to several factors, including:

• Hypoglycaemia, which can cause irritability and mood changes

• Gastrointestinal discomfort, which may affect overall wellbeing

• Changes in weight or appetite, which can sometimes influence mood and energy levels

• Underlying diabetes-related stress or adjustment to new medication

It is important to note that mood changes are not listed as a recognised side effect in the official Summary of Product Characteristics, and any such experiences should be discussed with a healthcare professional to identify potential causes.

Managing Mood Changes While Taking Rybelsus

If you notice mood swings, irritability, or changes in your emotional wellbeing while taking Rybelsus, there are several practical steps you can take to manage these symptoms and identify potential contributing factors.

Monitor your blood glucose levels regularly. Fluctuations in blood sugar, particularly hypoglycaemia, can significantly affect mood and cause irritability, anxiety, or confusion. If you experience symptoms such as shakiness, sweating, or sudden mood changes, check your blood glucose. If levels are low, follow Diabetes UK/NHS guidance for treating hypoglycaemia by consuming 15–20 grams of fast-acting carbohydrate (such as glucose tablets, fruit juice, or sugary sweets) and rechecking after 15 minutes.

Keep a symptom diary to track when mood changes occur in relation to medication timing, meals, and blood glucose readings. This information can help you and your GP identify patterns and determine whether the mood changes are related to Rybelsus, blood sugar fluctuations, or other factors.

Address gastrointestinal side effects, as persistent nausea, vomiting, or abdominal discomfort can negatively impact mood and quality of life. Strategies include:

• Eating smaller, more frequent meals

• Avoiding fatty, spicy, or rich foods

• Staying well hydrated

• Taking Rybelsus exactly as prescribed (with up to 120 ml water, swallowed whole, at least 30 minutes before the first food, drink, or other oral medicines of the day)

Maintain a healthy lifestyle with regular physical activity, adequate sleep, and stress management techniques. Exercise has been shown to improve both blood glucose control and mood in people with diabetes. NICE guidance (NG28) recommends that adults with type 2 diabetes engage in at least 150 minutes of moderate-intensity aerobic activity per week.

Communicate openly with your diabetes care team. If mood changes persist or worsen, do not discontinue Rybelsus without medical advice. Your GP or diabetes specialist nurse can review your treatment plan, adjust doses if necessary, or explore alternative medications if Rybelsus is not suitable for you. If you experience persistent low mood or anxiety, they may also suggest mental health support such as NHS Talking Therapies.

When to Contact Your GP About Rybelsus Side Effects

While many side effects of Rybelsus are mild and resolve with time, certain symptoms require prompt medical attention. You should contact your GP or diabetes care team if you experience:

Severe or persistent gastrointestinal symptoms, particularly if you have:

• Severe abdominal pain that does not improve

• Persistent vomiting that prevents you from keeping down food or fluids

• Signs of dehydration (dark urine, reduced urine output, dizziness, dry mouth)

• Symptoms suggestive of pancreatitis (severe, persistent abdominal pain radiating to the back, often accompanied by nausea and vomiting)

Signs of gallbladder disease, including:

• Pain in the right upper abdomen

• Fever

• Yellowing of the skin or eyes (jaundice)

Significant mood changes or mental health concerns, including:

• Persistent low mood, anxiety, or depression

• Mood swings that interfere with daily activities or relationships

• Thoughts of self-harm (seek urgent help via your GP, NHS 111, or emergency services)

Recurrent hypoglycaemia, especially if you experience frequent episodes of low blood sugar or are unaware of warning symptoms. Your medication regimen may need adjustment.

Allergic reactions, such as:

• Rash, itching, or hives

• Swelling of the face, lips, tongue, or throat

• Difficulty breathing (call 999 immediately)

Visual changes, particularly if you have pre-existing diabetic retinopathy. Report any changes in vision promptly to your GP or attend your regular diabetic eye screening appointments.

Unexplained weight loss that seems excessive or concerning.

If you are unsure whether a symptom requires medical attention, contact NHS 111 for advice or speak with your community pharmacist, who can provide guidance on managing side effects. Never stop taking Rybelsus abruptly without consulting your healthcare team, as this may affect your blood glucose control. Your GP can assess whether the benefits of continuing Rybelsus outweigh any side effects you are experiencing and discuss alternative treatment options if necessary.

You can report any suspected side effects to the MHRA Yellow Card Scheme at yellowcard.mhra.gov.uk or via the Yellow Card app. Regular follow-up appointments are essential to monitor your response to treatment and ensure optimal diabetes management.

Frequently Asked Questions