Rybelsus (semaglutide) is an oral GLP-1 receptor agonist used to treat type 2 diabetes in the UK. Whilst fatigue is not listed as a common side effect in the Summary of Product Characteristics, some patients do report feeling tired whilst taking this medication. Tiredness may arise from various factors, including the underlying diabetes itself, changes in eating patterns due to reduced appetite, gastrointestinal side effects, or the body adjusting to improved blood glucose control. If you experience persistent or troublesome tiredness on Rybelsus, it is important to discuss this with your GP or diabetes specialist nurse for proper assessment and guidance.

Can Rybelsus Make You Tired?

Rybelsus (semaglutide) is an oral glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for the treatment of type 2 diabetes mellitus. It works by mimicking the action of the naturally occurring hormone GLP-1, which stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon release, slows gastric emptying, and promotes satiety. These mechanisms help improve glycaemic control and often lead to weight reduction.

Fatigue is not listed as a common adverse reaction in the UK Summary of Product Characteristics (SmPC) for Rybelsus. The most frequently reported side effects include gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain, and constipation. These occur in a significant proportion of patients, particularly during dose titration.

However, some patients do report feeling tired whilst taking Rybelsus. It is important to recognise that tiredness can arise from multiple factors, including the underlying condition being treated (type 2 diabetes itself), changes in eating patterns due to reduced appetite, gastrointestinal side effects affecting nutrition, or concurrent medications. Additionally, improved glycaemic control may initially cause subtle physiological adjustments as the body adapts to more stable blood glucose levels.

If you are experiencing persistent or troublesome tiredness while taking Rybelsus, it is essential to discuss this with your GP or diabetes specialist nurse. They can assess whether the fatigue is related to the medication, your diabetes management, or other health factors, and provide appropriate guidance tailored to your individual circumstances.

Managing Tiredness While Taking Rybelsus

If you are experiencing tiredness whilst taking Rybelsus, there are several practical strategies that may help manage this symptom effectively whilst continuing your diabetes treatment.

Optimise your nutrition and hydration:

• Ensure you are consuming adequate calories despite reduced appetite, as severe calorie restriction can lead to fatigue

• Eat small, frequent, nutrient-dense meals throughout the day rather than large portions

• Maintain good hydration, aiming for 6–8 glasses of water daily (follow your clinician's advice if you have been advised to restrict fluids)

• Include complex carbohydrates, lean proteins, and healthy fats to sustain energy levels

• Consider keeping a food diary to identify if tiredness correlates with inadequate nutritional intake

Address gastrointestinal side effects:

Since nausea, vomiting, and diarrhoea are common with Rybelsus, these symptoms may indirectly contribute to fatigue by affecting your ability to eat properly or causing dehydration. Speak with your healthcare provider about strategies to minimise these effects, such as taking the medication correctly (on an empty stomach with no more than 120ml of plain water, swallowing the tablet whole without splitting, crushing or chewing, and waiting at least 30 minutes before eating, drinking or taking other oral medicines). Anti-emetic medications should only be used following clinical advice due to potential contraindications or interactions.

Monitor your blood glucose levels:

Both hypoglycaemia (low blood sugar) and hyperglycaemia (high blood sugar) can cause tiredness. Regular blood glucose monitoring can help identify patterns. The risk of hypoglycaemia is increased when Rybelsus is used alongside sulphonylureas or insulin. If you are experiencing frequent low blood glucose episodes, discuss dose adjustments with your diabetes team.

Maintain regular physical activity:

Whilst it may seem counterintuitive, regular moderate exercise can actually improve energy levels and reduce fatigue. The NHS recommends at least 150 minutes of moderate-intensity activity per week for adults with type 2 diabetes, plus muscle-strengthening activities on at least 2 days per week. Start gradually if you are not currently active, and consult your healthcare team before beginning any new exercise programme.

When to Seek Medical Advice About Fatigue

Whilst mild tiredness may be manageable with lifestyle adjustments, certain features warrant prompt medical assessment to rule out potentially serious underlying causes or complications.

Contact your GP or diabetes specialist nurse if you experience:

• Severe or worsening fatigue that significantly impacts your daily activities or quality of life

• Persistent tiredness that does not improve after several weeks despite self-management strategies

• Symptoms suggesting hypoglycaemia, including shakiness, sweating, confusion, palpitations, or hunger alongside tiredness

• Signs of dehydration, such as dark urine, dizziness, dry mouth, or reduced urine output, particularly if accompanied by vomiting or diarrhoea

• Unexplained weight loss beyond what would be expected from improved diabetes control

• New or worsening symptoms such as shortness of breath, chest pain, or palpitations

• Visual changes or deterioration, as rapid improvement in blood glucose can sometimes worsen diabetic retinopathy

• Right upper abdominal pain, fever, yellowing of skin/eyes or pale stools, which could indicate gallbladder disease (a known risk with GLP-1 receptor agonists)

Seek urgent medical attention (call 999 or attend A&E) if you develop:

• Severe abdominal pain that does not resolve, particularly if radiating to the back (potential pancreatitis)

• Signs of severe dehydration with inability to keep fluids down

• Altered consciousness or severe confusion

• Symptoms of diabetic ketoacidosis (though rare in type 2 diabetes), including excessive thirst, frequent urination, fruity breath odour, and rapid breathing

For urgent but non-life-threatening concerns, contact NHS 111 for advice.

Your healthcare provider may wish to investigate potential causes of fatigue through blood tests, including full blood count (to check for anaemia), thyroid function tests, vitamin B12, folate and ferritin levels, renal function, and HbA1c to assess overall diabetes control. According to NICE guidance on type 2 diabetes management, regular monitoring and individualised treatment adjustments are essential to optimise outcomes whilst minimising adverse effects.

If you suspect your tiredness may be a side effect of Rybelsus, you can report this through the MHRA Yellow Card scheme, which helps monitor medication safety.

Alternative Explanations for Tiredness on Rybelsus

When experiencing fatigue whilst taking Rybelsus, it is important to consider that tiredness may not be directly caused by the medication itself but rather by other factors related to your diabetes, general health, or lifestyle.

Diabetes-related causes:

Type 2 diabetes itself is a common cause of fatigue. Poor glycaemic control, whether blood glucose levels are too high or too low, can lead to tiredness. Hyperglycaemia causes the body to work harder to eliminate excess glucose through urine, leading to dehydration and energy depletion. Conversely, hypoglycaemia deprives the brain and muscles of their primary fuel source. Additionally, diabetes-related complications such as diabetic neuropathy, cardiovascular disease, or kidney impairment can contribute to persistent fatigue.

Nutritional deficiencies:

Patients with type 2 diabetes, particularly those taking metformin (often prescribed alongside Rybelsus), may develop vitamin B12 deficiency, which causes fatigue and weakness. The MHRA has issued a Drug Safety Update highlighting this risk, and testing should be considered if you are symptomatic. Iron deficiency anaemia is another common cause of tiredness that can be identified through blood tests. The appetite suppression caused by Rybelsus may inadvertently lead to inadequate intake of essential nutrients if dietary choices are not carefully managed. A referral to a dietitian may be helpful if this is a concern.

Concurrent medical conditions:

Many conditions commonly coexist with type 2 diabetes and cause fatigue, including:

• Hypothyroidism (underactive thyroid) – more common in people with diabetes than in the general population

• Obstructive sleep apnoea – more prevalent in individuals with obesity; discuss with your GP if you have symptoms such as loud snoring, breathing pauses during sleep, or excessive daytime sleepiness

• Depression and anxiety – psychological conditions frequently associated with chronic disease

• Chronic kidney disease – a potential complication of diabetes

• Cardiovascular disease – heart failure or coronary artery disease can cause fatigue

Medication interactions:

Review all your medications with your pharmacist or GP, as some drugs can cause tiredness as a side effect. Beta-blockers, certain blood pressure medications, antihistamines, and some pain medications are known to cause fatigue.

Lifestyle factors:

Poor sleep quality, inadequate physical activity, high stress levels, and excessive alcohol consumption can all contribute to persistent tiredness. A comprehensive assessment by your healthcare team can help identify and address these multiple potential contributors to fatigue, ensuring your diabetes treatment plan is optimised whilst maintaining your overall wellbeing and quality of life.

Frequently Asked Questions