Mounjaro (tirzepatide) is a dual GIP and GLP-1 receptor agonist licensed in the UK for type 2 diabetes and weight management. Whilst fatigue is not listed as a common adverse reaction in the UK Summary of Product Characteristics, some patients report tiredness during treatment. This may relate to reduced caloric intake, changes in blood glucose levels, gastrointestinal side effects, or metabolic adaptation rather than a direct drug effect. Understanding potential mechanisms and management strategies can help patients maintain energy levels whilst benefiting from Mounjaro's therapeutic effects. This article examines the relationship between Mounjaro and fatigue, offering practical guidance for patients and healthcare professionals.
Quick Answer: Mounjaro may indirectly cause tiredness through reduced caloric intake, blood glucose changes, gastrointestinal side effects, or metabolic adaptation, though fatigue is not listed as a common adverse reaction in UK prescribing information.
Mounjaro (tirzepatide) is a prescription medicine licensed in the UK for the treatment of type 2 diabetes mellitus. In the UK, tirzepatide is also available under the brand name Zepbound for weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity, subject to specific NICE criteria for NHS use. As a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, Mounjaro works by mimicking naturally occurring hormones that regulate blood sugar levels and appetite.
Fatigue, or persistent tiredness, is a concern that some patients report when taking Mounjaro. It is important to note that fatigue is not listed among the common adverse reactions in the UK Summary of Product Characteristics (SmPC). However, clinical experience suggests that some individuals may experience tiredness during treatment, which could be related to indirect effects of the medication rather than a direct adverse reaction. It is important to distinguish between normal tiredness related to lifestyle factors and fatigue that may be connected to indirect effects of the medication or underlying metabolic changes.
Understanding whether Mounjaro might indirectly contribute to tiredness requires consideration of multiple factors, including the drug's mechanism of action, individual patient characteristics, dietary changes associated with reduced appetite, and the body's adjustment to improved glycaemic control. For many patients, any fatigue experienced may be temporary, particularly during the initial weeks of treatment, whilst others may experience more persistent tiredness that warrants medical review.
This article examines the potential relationship between Mounjaro and fatigue, explores possible mechanisms, and provides practical guidance for patients and healthcare professionals on managing tiredness whilst taking this medication.
Several mechanisms may potentially explain why some patients experience fatigue whilst taking Mounjaro, though there is no direct link established in clinical trials as a common adverse effect in the UK SmPC. Understanding these potential contributing factors can help patients and clinicians identify possible causes.
Reduced caloric intake is one of the most significant potential factors. Mounjaro works partly by reducing appetite and slowing gastric emptying, which often leads to substantially decreased food consumption. When caloric intake drops significantly—particularly if the reduction is rapid—the body may experience temporary fatigue as it adapts to lower energy availability. Patients who reduce their intake too drastically may not be consuming adequate nutrients to maintain normal energy levels.
Changes in blood glucose levels represent another important consideration. For patients with type 2 diabetes, Mounjaro improves glycaemic control by enhancing insulin secretion and reducing glucagon release in a glucose-dependent manner. Whilst this therapeutic effect is beneficial, some patients may experience relative hypoglycaemia—blood sugar levels that, whilst not clinically low (defined in the UK as <4.0 mmol/L), are lower than the body has become accustomed to. This adjustment period can manifest as tiredness, particularly in patients whose glucose levels were previously poorly controlled.
Gastrointestinal side effects such as nausea, vomiting, and diarrhoea are common with Mounjaro, as noted in the SmPC, especially during dose escalation. These symptoms can lead to reduced food and fluid intake, potentially causing dehydration and electrolyte imbalances, both of which contribute to fatigue. Additionally, disrupted sleep due to gastrointestinal discomfort may result in daytime tiredness.
Metabolic adaptation during weight loss may also play a role. As the body loses weight, metabolic rate can decrease, and hormonal changes occur that may temporarily affect energy levels. This is a normal physiological response but can be perceived as increased tiredness during the weight loss phase.
If you experience tiredness whilst taking Mounjaro, several practical strategies may help manage this symptom effectively whilst continuing to benefit from the medication's therapeutic effects.
Ensure adequate nutrition despite reduced appetite. Whilst Mounjaro naturally decreases hunger, it remains essential to consume sufficient calories and nutrients to support normal bodily functions. Focus on nutrient-dense foods including:
Lean proteins (chicken, fish, eggs, legumes) to maintain muscle mass
Complex carbohydrates (whole grains, vegetables) for sustained energy
Healthy fats (avocado, nuts, olive oil) for hormone production
Adequate vitamins and minerals through varied fruit and vegetables
Consider eating smaller, more frequent meals if large portions feel overwhelming. A registered dietitian can provide personalised guidance on maintaining balanced nutrition whilst managing reduced appetite.
Stay well hydrated by drinking adequate fluids throughout the day. Dehydration can significantly worsen fatigue, particularly if you are experiencing gastrointestinal side effects. Aim for 6-8 glasses of fluid daily (approximately 1.2 litres), and more in hot weather or if you're experiencing vomiting or diarrhoea.
Monitor your blood glucose levels if you have diabetes, especially during the first few months of treatment. Keep a record of readings and note any correlation between low-normal glucose levels and feelings of tiredness. Share this information with your healthcare team. Remember that a blood glucose level below 4.0 mmol/L is considered hypoglycaemia in the UK and requires treatment.
Prioritise sleep hygiene by maintaining regular sleep schedules, creating a comfortable sleep environment, and avoiding screens before bedtime. Quality sleep is essential for managing fatigue and supporting overall health during treatment.
Incorporate gentle physical activity as tolerated. Whilst it may seem counterintuitive when feeling tired, regular moderate exercise can actually improve energy levels over time. Start with short walks and gradually increase activity as your body adapts to the medication.
Follow the correct dosing schedule. Mounjaro is administered once weekly on the same day each week. The time of day can be flexible, but if you need to change your weekly injection day, ensure there are at least 3 days between doses. If you miss a dose, you can take it within 4 days of the scheduled time; otherwise, skip that dose and take the next one as planned. Some patients find that taking it on a day when they can rest if needed (such as a weekend) helps manage any immediate side effects.
Whilst mild fatigue may be manageable with lifestyle adjustments, certain situations warrant prompt medical review. Contact your GP or diabetes specialist nurse if you experience:
Severe or worsening fatigue that significantly impacts your daily activities, work, or quality of life
Persistent tiredness lasting beyond the first 8–12 weeks of treatment, as initial side effects typically improve as the body adjusts
Symptoms of hypoglycaemia including shakiness, sweating, confusion, rapid heartbeat, or extreme tiredness, particularly if you are taking Mounjaro alongside other diabetes medications such as sulphonylureas or insulin. In the UK, hypoglycaemia is defined as a blood glucose level below 4.0 mmol/L
Signs of dehydration such as dark urine, dizziness, dry mouth, or reduced urination, especially if accompanied by ongoing gastrointestinal symptoms
Unexplained weight loss that seems excessive or is occurring too rapidly (more than 1–2 kg per week consistently)
Call 999 or go to A&E if you develop:
Severe abdominal pain that doesn't resolve, which could indicate pancreatitis (a rare but serious side effect)
Signs of severe allergic reaction such as difficulty breathing, severe rash, or swelling of the face or throat
Symptoms of diabetic ketoacidosis (particularly during acute illness or if insulin doses have been reduced) including excessive thirst, frequent urination, nausea, vomiting, abdominal pain, or fruity-smelling breath
Contact your GP promptly if you notice:
Your healthcare provider may wish to:
Review your current dose and consider adjusting the titration schedule
Check blood tests including full blood count, thyroid function, kidney function, ferritin, and electrolytes to rule out other causes of fatigue (vitamin B12 may also be checked, particularly if you are taking metformin)
Assess your overall diabetes management and adjust other medications if needed
Evaluate your nutritional intake and refer you to a dietitian
Consider whether Mounjaro remains the most appropriate treatment option for you
Never stop taking Mounjaro abruptly without consulting your healthcare team, as this may affect your diabetes control or weight management progress.
For non-emergency advice when your GP is unavailable, contact NHS 111.
Understanding the broader side effect profile of Mounjaro helps patients recognise what to expect and distinguish fatigue from other medication-related symptoms.
Gastrointestinal effects are the most frequently reported adverse reactions with Mounjaro. According to the UK SmPC, these include:
Nausea (very common, affecting more than 1 in 10 patients) – usually most pronounced during dose escalation and often improves with time
Diarrhoea (very common) – can contribute to dehydration and electrolyte imbalance if severe
Vomiting (very common) – typically mild to moderate and transient
Constipation (common, affecting up to 1 in 10 patients) – may occur due to slowed gastric emptying
Abdominal pain or discomfort (common) – usually mild but should be monitored
Decreased appetite (very common) – this is partly how the medication works but can be pronounced in some individuals
These gastrointestinal symptoms are generally most common when starting treatment or increasing the dose, and tend to diminish over several weeks as the body adjusts. The frequency of these effects increases with higher doses.
Hypoglycaemia (low blood sugar, below 4.0 mmol/L) can occur, particularly when Mounjaro is used in combination with insulin or sulphonylureas. Symptoms include trembling, sweating, anxiety, confusion, and tiredness. Your doctor may need to reduce doses of these other medications when starting Mounjaro.
Injection site reactions such as redness, itching, or swelling at the injection site are usually mild and resolve quickly. Rotating injection sites (abdomen, thigh, or upper arm) can help minimise these reactions.
Other reported side effects include:
Headache
Dizziness
Increased heart rate
Indigestion or acid reflux
Flatulence and bloating
Rare but serious side effects require immediate medical attention and include acute pancreatitis (severe abdominal pain radiating to the back), severe allergic reactions, gallbladder problems (presenting as right upper quadrant pain, fever, or jaundice), and kidney injury (particularly in the context of severe dehydration from vomiting or diarrhoea).
The MHRA and EMA continue to monitor the safety profile of tirzepatide. Patients are encouraged to report any suspected side effects via the MHRA Yellow Card Scheme (www.mhra.gov.uk/yellowcard or via the Yellow Card app), contributing to ongoing pharmacovigilance and medication safety. Most patients tolerate Mounjaro well, and side effects often improve significantly after the initial adjustment period, allowing patients to benefit from improved glycaemic control and weight management.
Fatigue is not listed as a common adverse reaction in the UK Summary of Product Characteristics for Mounjaro. However, some patients may experience tiredness indirectly through reduced caloric intake, changes in blood glucose levels, or gastrointestinal side effects such as nausea and vomiting.
To manage tiredness, ensure adequate nutrition with nutrient-dense foods despite reduced appetite, stay well hydrated with 6–8 glasses of fluid daily, monitor blood glucose levels if you have diabetes, prioritise quality sleep, and incorporate gentle physical activity as tolerated.
Contact your GP if you experience severe or worsening fatigue affecting daily activities, persistent tiredness beyond 8–12 weeks, symptoms of hypoglycaemia (blood glucose below 4.0 mmol/L), signs of dehydration, or unexplained rapid weight loss. Your healthcare provider can review your dose, check blood tests, and assess whether Mounjaro remains appropriate for you.
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