Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for treating type 2 diabetes mellitus. Whilst lethargy is not among the most commonly reported adverse effects in the Summary of Product Characteristics, some patients do experience unusual tiredness during treatment. Fatigue may arise indirectly through gastrointestinal disturbances, reduced caloric intake, or blood glucose fluctuations. Understanding the potential causes and management strategies is essential for patients and healthcare professionals to optimise treatment outcomes and maintain quality of life whilst using this medication.

Does Ozempic Make You Lethargic?

Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for the treatment of type 2 diabetes mellitus. It should be noted that Wegovy (also semaglutide, but at a higher dose of 2.4mg) is the licensed product for weight management, not Ozempic.

Whilst lethargy and fatigue are not listed among the most common adverse effects of Ozempic in the Summary of Product Characteristics (SmPC) approved by the Medicines and Healthcare products Regulatory Agency (MHRA), some patients do report feeling unusually tired during treatment.

Clinical trial data and post-marketing surveillance indicate that fatigue occurs in a small proportion of Ozempic users. The most commonly reported adverse reactions include gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and constipation, which affect a significant number of patients, particularly during dose escalation. These gastrointestinal disturbances can indirectly contribute to feelings of tiredness and reduced energy.

The physiological changes induced by the medication—including alterations in blood glucose levels, reduced caloric intake due to appetite suppression, and gastrointestinal side effects—may create conditions that lead to fatigue. It is important to distinguish between true lethargy (a lack of energy or motivation) and general tiredness, which may have multiple contributing factors.

Patients experiencing persistent or severe fatigue whilst taking Ozempic should discuss this with their GP or diabetes specialist nurse. Seek urgent medical attention if you experience severe abdominal pain (which may radiate to the back), persistent vomiting, or jaundice (yellowing of the skin or eyes), as these could indicate serious conditions such as pancreatitis or gallbladder disease.

Why Ozempic May Cause Tiredness or Fatigue

Understanding the potential mechanisms by which Ozempic might contribute to tiredness requires consideration of both its pharmacological action and the metabolic changes it induces. Semaglutide works by mimicking the action of endogenous GLP-1, a hormone that enhances insulin secretion in a glucose-dependent manner, suppresses glucagon release, slows gastric emptying, and reduces appetite through central nervous system pathways.

Reduced caloric intake is one of the primary ways Ozempic helps improve glycaemic control. However, a significant decrease in energy consumption—particularly if it occurs rapidly or results in inadequate nutrition—can lead to feelings of fatigue and low energy. Patients may inadvertently consume insufficient calories, protein, or essential micronutrients, all of which are necessary for maintaining normal energy levels and metabolic function.

Gastrointestinal side effects, particularly nausea and vomiting, are common during the initial weeks of treatment and following dose increases. These symptoms can reduce food intake further, disrupt sleep, and contribute to dehydration, all of which exacerbate tiredness. Significant dehydration from vomiting or diarrhoea can potentially lead to kidney problems, so it's important to maintain adequate fluid intake and seek medical advice if you're unable to keep fluids down.

Another consideration is the impact on blood glucose levels. The risk of hypoglycaemia (low blood sugar) with Ozempic alone is low. However, this risk increases when used in combination with other glucose-lowering medications such as sulfonylureas or insulin. Hypoglycaemia is a well-recognised cause of fatigue, weakness, and lethargy. Even in the absence of frank hypoglycaemia, fluctuations in blood glucose may affect energy levels and cognitive function, contributing to a sense of tiredness throughout the day.

Alternative Explanations for Fatigue During Treatment

When assessing fatigue in a patient taking Ozempic, it is essential to consider alternative or coexisting explanations that may not be directly related to the medication. A comprehensive clinical evaluation should explore other potential causes, as fatigue is a non-specific symptom with a broad differential diagnosis.

Underlying type 2 diabetes itself is a common cause of tiredness. Poor glycaemic control, whether due to hyperglycaemia or hypoglycaemia, can result in significant fatigue. Patients who are newly diagnosed or whose diabetes management is being optimised may experience fluctuations in energy levels as their blood glucose stabilises. Additionally, complications of diabetes—such as diabetic neuropathy, nephropathy, or cardiovascular disease—can contribute to reduced stamina and increased tiredness.

Nutritional deficiencies may develop if dietary intake becomes inadequate due to appetite suppression. Deficiencies in iron, vitamin B12, folate, or vitamin D are all associated with fatigue and may require investigation through blood tests. Patients experiencing significant weight loss or dietary changes may benefit from dietetic input to ensure nutritional adequacy.

Thyroid dysfunction should be considered in patients with persistent fatigue, as it can present with lethargy, weight changes, and low mood. Routine thyroid function tests (TFTs) may be appropriate if fatigue persists. Similarly, anaemia, whether due to chronic disease, nutritional deficiency, or other causes, is a common and treatable cause of tiredness that warrants investigation with a full blood count.

Sleep disturbances, including obstructive sleep apnoea (which is common in individuals with obesity and type 2 diabetes), depression, anxiety, and other mental health conditions can all manifest as daytime fatigue. A holistic assessment should include questions about sleep quality, mood, and psychosocial stressors. Referral to appropriate services, such as sleep clinics or psychological support, may be necessary depending on clinical findings.

How to Manage Lethargy While Taking Ozempic

Effective management of lethargy during Ozempic treatment involves a combination of lifestyle modifications, monitoring, and, where necessary, medical intervention. The first step is to ensure that the fatigue is not due to a serious underlying condition that requires urgent attention.

Optimising nutritional intake is paramount. Patients should be encouraged to consume a balanced diet that meets their energy and micronutrient needs, even if appetite is reduced. Small, frequent meals that are nutrient-dense can help maintain energy levels without overwhelming the digestive system. Adequate protein intake is particularly important to preserve muscle mass during weight loss. Referral to a dietitian with expertise in diabetes management can provide tailored advice and support.

Hydration is often overlooked but essential, especially if gastrointestinal side effects such as vomiting or diarrhoea are present. Dehydration can significantly worsen fatigue and should be addressed promptly. Patients should be advised to drink plenty of water throughout the day and to seek medical advice if they are unable to maintain adequate fluid intake.

Monitoring blood glucose levels may be helpful if you are taking Ozempic with insulin or a sulfonylurea, or if you are experiencing symptoms of hypoglycaemia. Routine self-monitoring is generally not required for patients on Ozempic alone, in line with NICE guidance. Patients using Ozempic in combination with other glucose-lowering therapies should discuss their regimen with their healthcare team to minimise the risk of hypoglycaemia.

Gradual dose escalation as per the SmPC is recommended to minimise side effects. Ozempic is typically started at 0.25mg once weekly for four weeks, then increased to 0.5mg once weekly, with further increases only under prescriber supervision. If fatigue is severe, it may be appropriate to slow the rate of dose increase or temporarily maintain a lower dose whilst the body adjusts.

Physical activity, even in modest amounts, can improve energy levels and overall well-being. Patients should be encouraged to engage in regular, moderate exercise as tolerated.

When to seek medical advice: Contact your GP or diabetes care team if fatigue is severe, persistent, or accompanied by other concerning symptoms. Seek urgent medical attention for severe abdominal pain (especially if radiating to the back), persistent vomiting, jaundice, or inability to keep fluids down, as these may indicate serious conditions such as pancreatitis or gallbladder disease. Blood tests to assess for anaemia, thyroid dysfunction, vitamin deficiencies, and renal function may be warranted. If lethargy significantly impairs quality of life or daily functioning, a review of the treatment plan may be appropriate.

Suspected side effects can be reported via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

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