Mounjaro and Restless Legs: Causes, Management and When to Seek Help

Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor agonist licensed in the UK for type 2 diabetes and weight management. Whilst gastrointestinal side effects such as nausea and diarrhoea are well documented, some patients have reported leg discomfort resembling restless legs during treatment. Restless legs syndrome is not listed as a recognised adverse reaction in UK regulatory documentation for Mounjaro. This article examines the potential relationship between Mounjaro and restless leg symptoms, explores possible contributing factors, and provides guidance on management and when to seek medical advice, in line with NICE and MHRA recommendations.

What Is Mounjaro and How Does It Work?

Mounjaro (tirzepatide) is a prescription medicine licensed in the UK for the treatment of type 2 diabetes mellitus and, more recently, for weight management in adults with obesity or overweight with weight-related comorbidities. It belongs to a novel class of medications known as dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. By activating both GIP and GLP-1 receptors, Mounjaro enhances insulin secretion in response to meals, suppresses glucagon release, slows gastric emptying, and reduces appetite—mechanisms that collectively improve glycaemic control and promote weight loss.

Mounjaro is administered as a once-weekly subcutaneous injection, typically starting at a low dose (2.5 mg) and gradually titrated upwards at 4-week intervals (to 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg) to minimise gastrointestinal side effects and optimise therapeutic benefit. The Medicines and Healthcare products Regulatory Agency (MHRA) approved Mounjaro for type 2 diabetes in October 2022, and the National Institute for Health and Care Excellence (NICE) has issued guidance on its use within the NHS for both diabetes (TA870) and weight management (TA906), subject to specific eligibility criteria.

As with all medicines, Mounjaro can cause side effects. According to the UK Summary of Product Characteristics (SmPC), the most commonly reported adverse reactions include nausea, diarrhoea, vomiting, constipation, abdominal pain, and decreased appetite. These gastrointestinal symptoms are usually mild to moderate and tend to diminish over time. However, patients and healthcare professionals have occasionally reported other symptoms during treatment, including sensations in the legs that may resemble restless legs. It is important to note that restless legs syndrome is not listed as a recognised adverse reaction in the UK SmPC or European Public Assessment Report (EPAR) for Mounjaro. Suspected adverse drug reactions should be reported via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

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Why Might Restless Legs Occur During Mounjaro Treatment?

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a neurological condition characterised by an irresistible urge to move the legs, often accompanied by uncomfortable sensations such as tingling, crawling, or aching. Symptoms typically worsen during periods of rest or inactivity, particularly in the evening or at night, and are temporarily relieved by movement. While RLS has well-established associations with iron deficiency, chronic kidney disease, pregnancy, and certain medications, there is currently no official, evidence-based link between Mounjaro (tirzepatide) and restless legs syndrome in the published literature or regulatory documentation.

Nevertheless, anecdotal reports from patients taking GLP-1 receptor agonists and dual GIP/GLP-1 agonists have occasionally mentioned leg discomfort or sensations that could be interpreted as restless legs. Several hypothetical mechanisms might potentially contribute to such symptoms, though these remain speculative:

• Nutritional considerations: Mounjaro's appetite-suppressing effects and associated weight loss may lead to reduced dietary intake of nutrients, including iron and vitamin B12—both of which are implicated in RLS pathophysiology. People with type 2 diabetes taking metformin may already have reduced vitamin B12 levels, which could be a confounding factor.

• Metabolic changes: Rapid weight loss may alter various metabolic parameters, though a direct link to RLS symptoms has not been established.

• Electrolyte changes: Significant gastrointestinal side effects (vomiting, diarrhoea) could potentially lead to dehydration or electrolyte disturbances, which might influence neurological symptoms.

• Sleep disruption: Gastrointestinal side effects or changes in eating patterns may interfere with sleep quality, which can exacerbate or unmask pre-existing RLS.

• Coincidental factors: Patients starting Mounjaro often have comorbidities (type 2 diabetes, obesity, cardiovascular disease) that independently increase RLS risk.

It is essential to recognise that correlation does not imply causation. If restless leg symptoms emerge during Mounjaro treatment, a thorough clinical assessment is needed to identify underlying or contributing factors, following UK guidance such as NICE Clinical Knowledge Summary (CKS) for Restless legs syndrome.

Managing Restless Leg Symptoms While Taking Mounjaro

If you experience restless leg symptoms while taking Mounjaro, several self-care strategies and lifestyle modifications may help alleviate discomfort:

• Maintain a balanced diet: Despite reduced appetite, ensure adequate intake of iron-rich foods (red meat, poultry, fish, lentils, fortified cereals), folate (leafy greens, beans, citrus), and vitamin B12 (meat, dairy, fortified products). Do not start iron supplements without first having blood tests to confirm deficiency, as inappropriate supplementation carries risks.

• Stay hydrated: Dehydration may worsen leg discomfort. Drink plenty of water throughout the day. If you experience significant vomiting or diarrhoea, contact your healthcare provider as you may need assessment of your kidney function and electrolytes (sodium, potassium).

• Engage in regular, moderate exercise: Gentle physical activity—such as walking, cycling, or stretching—can improve circulation and reduce RLS symptoms. Avoid vigorous exercise close to bedtime, as this may worsen symptoms in some individuals.

• Establish good sleep hygiene: Maintain a consistent sleep schedule, keep your bedroom cool and dark, and avoid caffeine, alcohol, and heavy meals in the evening. These measures can improve sleep quality and reduce nocturnal leg discomfort.

• Apply heat or cold: Some people find relief by using a warm bath, heating pad, or cold compress on the legs before bed.

• Avoid known RLS triggers: Certain medications (e.g., antihistamines, some antidepressants, antipsychotics) and substances (caffeine, nicotine) can exacerbate RLS. Review your medication list with your GP or pharmacist.

Do not stop or adjust your Mounjaro dose without medical advice. Abrupt discontinuation may affect your diabetes control or weight management goals. If symptoms are troublesome or persistent, contact your healthcare team for a comprehensive evaluation and tailored management plan.

When to Speak to Your GP About Restless Legs on Mounjaro

While mild, transient leg discomfort may not require immediate medical attention, you should contact your GP or diabetes specialist nurse if:

• Restless leg symptoms are severe, persistent, or worsening, significantly affecting your sleep, daily functioning, or quality of life.

• You experience additional neurological symptoms such as numbness, weakness, pain, or changes in coordination, which may indicate peripheral neuropathy or another condition requiring investigation.

• You have signs of nutritional deficiency, including fatigue, pallor, shortness of breath, or cognitive changes, which may warrant blood tests (full blood count, ferritin, vitamin B12, folate).

• You are concerned about the balance of benefits and side effects of Mounjaro and wish to discuss alternative treatment options.

Seek urgent medical attention if you develop:

• Unilateral leg swelling, redness, warmth or severe calf pain (possible deep vein thrombosis)

• Sudden severe weakness or numbness

• Back pain with bladder or bowel dysfunction

Your GP may arrange investigations to identify or exclude underlying causes of RLS, such as:

• Blood tests: To assess iron stores (serum ferritin—treatment may be considered if <75 µg/L), vitamin B12, folate, renal function (eGFR), and thyroid function (TSH).

• Medication review: To identify any drugs that may contribute to RLS and consider alternatives if appropriate.

• Referral to a specialist: If RLS is confirmed and does not respond to initial management, referral to a neurologist or sleep specialist may be considered for further assessment and treatment, which may include:

• Iron supplementation if deficiency is confirmed
• Dopamine agonists (e.g., ropinirole, pramipexole), though these carry risks of augmentation (symptom worsening) and impulse control disorders
• Alpha-2-delta ligands (e.g., gabapentin, pregabalin), which are used off-label for RLS in the UK and carry risks of dependence and sedation

The NICE Clinical Knowledge Summary (CKS) on Restless legs syndrome recommends a stepwise approach, starting with identification and correction of contributing factors (e.g., iron deficiency), followed by non-pharmacological measures and, if necessary, pharmacological treatment tailored to symptom severity and patient preference. Your healthcare team will work with you to ensure that your diabetes or weight management treatment remains effective while addressing any troublesome symptoms that arise.

If you suspect Mounjaro may be contributing to your symptoms, report this through the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

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