Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor agonist licensed in the UK for type 2 diabetes and weight management. Many patients with a single kidney wonder whether this medication is safe for them. Whilst tirzepatide is primarily metabolised via proteolytic cleavage rather than renal excretion, individuals relying on one kidney require careful assessment and monitoring. This article examines the safety, monitoring requirements, and prescribing considerations for Mounjaro in patients with a single functioning kidney, drawing on UK regulatory guidance and clinical evidence to support informed decision-making.

Understanding Mounjaro and Kidney Function

Mounjaro (tirzepatide) is a once-weekly injectable medication licensed in the UK for the treatment of type 2 diabetes mellitus and for weight management in adults with obesity or overweight with weight-related comorbidities. It belongs to a novel class of medicines 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 a glucose-dependent manner, suppresses glucagon release, slows gastric emptying, and reduces appetite—mechanisms that collectively improve glycaemic control and promote weight loss.

The kidneys play a vital role in maintaining metabolic homeostasis, regulating fluid and electrolyte balance, and eliminating waste products and certain medications from the body. Individuals living with a single functioning kidney—whether due to congenital absence (renal agenesis), surgical removal (nephrectomy), or loss of function from disease—rely entirely on one kidney to perform these essential tasks. While a single healthy kidney can often compensate adequately, any additional metabolic or pharmacological stress warrants careful consideration.

Tirzepatide is primarily metabolised via proteolytic cleavage and does not rely heavily on renal excretion for elimination. However, the kidneys remain central to managing the metabolic effects of diabetes and obesity, conditions for which Mounjaro is prescribed. Understanding how Mounjaro interacts with renal physiology is important for patients with a single kidney, as they may be at risk of dehydration or acute kidney injury if significant gastrointestinal side effects occur.

Safety of Mounjaro in Patients with One Kidney

Current evidence suggests that Mounjaro can be used in patients with reduced kidney function, including those with a single kidney, provided that renal function is stable and appropriately monitored. The Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have not issued specific contraindications for tirzepatide use in individuals with one kidney. Clinical trials of tirzepatide included participants across a spectrum of renal function, including those with moderate chronic kidney disease (CKD stage 3), and no significant safety signals emerged that would preclude its use in this population.

Importantly, no dose adjustment is required in renal impairment (including severe impairment). Clinical experience in patients on dialysis is limited, and specialist input is advised in these cases. Tirzepatide is metabolised predominantly through peptidase-mediated pathways rather than renal excretion. However, individuals with a single kidney should use any medication that affects fluid balance, appetite, or gastrointestinal function cautiously.

There is no official link between Mounjaro and direct nephrotoxicity. However, the gastrointestinal side effects commonly associated with GLP-1 receptor agonists—such as nausea, vomiting, and diarrhoea—can lead to dehydration and prerenal acute kidney injury, particularly in patients whose renal reserve is already limited. Additionally, there is a risk of gallbladder disease (cholelithiasis and cholecystitis) with GLP-1/GIP agonists. For these reasons, prescribers must assess baseline kidney function, ensure adequate hydration, and provide clear safety advice to patients with a single kidney before initiating treatment.

Monitoring and Precautions for Single Kidney Patients

Patients with a single kidney who are prescribed Mounjaro require individualised monitoring and proactive management to minimise risks and optimise therapeutic outcomes. Before starting tirzepatide, a comprehensive assessment should include:

• Baseline renal function tests: Measure serum creatinine and calculate eGFR to establish a reference point.

• Urine albumin:creatinine ratio (ACR): Screen for albuminuria as an early marker of kidney disease.

• Blood pressure measurement: Hypertension is a common comorbidity and a risk factor for CKD progression.

• Review of concomitant medications: Identify drugs that may affect renal function, such as diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), or non-steroidal anti-inflammatory drugs (NSAIDs).

Once treatment is initiated, regular follow-up is essential. NICE guidance recommends monitoring frequency based on CKD stage and clinical stability—typically annually for those with normal function, but more frequent assessments (every 3-6 months) for those with reduced eGFR (<60 mL/min/1.73m²) or rising ACR, particularly during dose escalation or if gastrointestinal side effects are prominent.

Patients should be counselled on the importance of maintaining adequate hydration, especially during the initial weeks of therapy when nausea and reduced appetite are most common. Practical advice includes sipping water regularly throughout the day, avoiding excessive caffeine or alcohol, and recognising early signs of dehydration such as dark urine, dizziness, or reduced urine output.

If severe vomiting or diarrhoea occurs, patients should be advised to seek medical review promptly, temporarily withhold tirzepatide, and review other medications that might affect kidney function. This 'sick day' approach can help prevent acute kidney injury.

Women using oral contraceptives should be advised to use additional contraception for 4 weeks after starting tirzepatide and for 4 weeks after each dose increase, or consider non-oral contraceptive methods, as tirzepatide may reduce the effectiveness of oral contraceptives.

Potential Risks and Side Effects

While Mounjaro is generally well tolerated, patients with a single kidney may be more vulnerable to certain adverse effects due to their reduced renal reserve. The most common side effects of tirzepatide are gastrointestinal in nature and include:

• Nausea and vomiting: Very common, particularly during dose titration.

• Diarrhoea: Common, can lead to fluid and electrolyte losses.

• Abdominal discomfort and reduced appetite: Common, may contribute to inadequate oral intake.

These symptoms, which are typically dose-dependent and often improve with time, can precipitate dehydration and prerenal acute kidney injury in susceptible individuals. Patients with one kidney have less capacity to compensate for volume depletion, making vigilant hydration and early intervention critical.

Another consideration is the potential for hypoglycaemia, especially when Mounjaro is used in combination with insulin or sulfonylureas. Dose adjustments of these concomitant medications are often necessary to reduce this risk. Patients should be educated on recognising and treating hypoglycaemia promptly.

Gallbladder disease (cholelithiasis and cholecystitis) has been reported with GLP-1 receptor agonists. Patients should seek urgent medical attention if they experience symptoms such as right upper-quadrant pain, fever, or jaundice.

Pancreatitis is a rare but serious adverse effect. Patients should be advised to stop tirzepatide and seek urgent medical attention if they experience severe, persistent abdominal pain radiating to the back, as pancreatitis can lead to systemic complications, including acute kidney injury.

Patients with pre-existing diabetic retinopathy should be monitored closely, as rapid improvement in glycaemic control may be associated with temporary worsening of retinopathy.

Finally, there have been post-marketing reports of acute kidney injury in patients treated with GLP-1 receptor agonists, often in the context of severe dehydration. While there is no evidence that tirzepatide is directly nephrotoxic, the indirect effects of gastrointestinal side effects underscore the importance of patient education and monitoring.

Patients should be encouraged to report any suspected side effects via the MHRA Yellow Card Scheme.

Clinical Guidance and Prescribing Considerations

Prescribing Mounjaro to patients with a single kidney requires a risk-benefit assessment tailored to the individual's clinical context. NICE guidance on the management of type 2 diabetes and obesity emphasises the importance of personalised care, taking into account comorbidities, renal function, and patient preferences.

Key prescribing considerations include:

• Renal function: No dose adjustment is required in renal impairment, including severe impairment. However, clinical experience in patients on dialysis is limited, and specialist nephrology input is recommended in these cases.

• Gradual dose titration: Starting at the lowest dose (2.5 mg once weekly for 4 weeks), then increasing to 5 mg, with further 2.5 mg increments as tolerated up to the maximum dose. This approach can help minimise gastrointestinal side effects.

• Concomitant medications: Review and, if necessary, adjust doses of other glucose-lowering agents (e.g., sulfonylureas, insulin) to reduce hypoglycaemia risk. Consider the nephroprotective benefits of SGLT2 inhibitors or ACE inhibitors/ARBs in line with NICE guidance for diabetes and CKD.

• Contraception advice: Women using oral contraceptives should use additional contraception for 4 weeks after starting tirzepatide and for 4 weeks after each dose increase, or consider non-oral methods.

• Patient education: Provide clear written and verbal information on recognising and managing side effects, maintaining hydration, and when to seek medical advice.

Shared decision-making is paramount. Patients should be informed of the potential benefits of Mounjaro—including improved glycaemic control, weight loss, and possible cardiovascular benefits—as well as the risks, particularly in the context of having a single kidney. Engaging patients in their care plan enhances adherence and safety.

When to Seek Medical Advice

Patients with a single kidney using Mounjaro should be empowered to recognise warning signs that require prompt medical attention. Immediate contact with a GP, NHS 111, or healthcare provider is advised if any of the following occur:

• Persistent vomiting or diarrhoea: Especially if lasting more than 24 hours, as this increases the risk of dehydration and acute kidney injury. Temporarily stop tirzepatide and seek same-day medical advice.

• Signs of dehydration: Including dark urine, reduced urine output, dizziness, dry mouth, or feeling faint.

• Severe abdominal pain: Particularly if radiating to the back, which may indicate pancreatitis. Stop tirzepatide immediately and seek urgent medical attention.

• Right upper-quadrant pain, fever, or jaundice: These may indicate gallbladder problems and require prompt assessment.

• Symptoms of hypoglycaemia: Such as sweating, tremor, confusion, or palpitations, especially if recurrent.

• Unexplained swelling: Oedema in the legs or face may suggest fluid retention or worsening kidney function.

• Severe chest pain or severe breathlessness: Call 999 immediately for these potentially life-threatening symptoms.

Routine follow-up appointments should not be missed, as they provide an opportunity to monitor renal function, review medication tolerability, and adjust treatment as needed. Patients should also inform their healthcare team of any new medications, over-the-counter drugs, or herbal supplements, as these may interact with Mounjaro or affect kidney function.

In summary, while Mounjaro can be used safely in many patients with a single kidney, close monitoring, patient education, and individualised care are essential to minimise risks and maximise therapeutic benefit. Open communication between patients and healthcare professionals is the cornerstone of safe and effective treatment.

Frequently Asked Questions