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Mounjaro (tirzepatide) is a dual GIP and GLP-1 receptor agonist licensed in the UK for type 2 diabetes and weight management in adults with obesity. Whilst Mounjaro significantly improves glycaemic control and facilitates substantial weight loss, questions have emerged about whether it influences cortisol levels—the body's primary stress hormone. Cortisol dysregulation is often associated with obesity and metabolic syndrome, conditions for which Mounjaro is prescribed. This article examines the current evidence on Mounjaro's potential effects on cortisol, explores the relationship between weight loss and hormonal balance, and clarifies when specialist endocrine assessment is needed.
Quick Answer: There is currently no established clinical evidence that Mounjaro (tirzepatide) directly lowers cortisol levels or treats cortisol-related disorders.
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 is administered as a once-weekly subcutaneous injection and belongs to a class of medications known as dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists.
The mechanism of action of Mounjaro involves mimicking two naturally occurring incretin hormones that play crucial roles in glucose regulation and appetite control. GLP-1 stimulates insulin secretion when blood glucose levels are elevated, suppresses glucagon release (which reduces glucose production by the liver), slows gastric emptying, and promotes satiety. GIP also enhances insulin secretion and may have effects on fat metabolism. By activating both pathways, tirzepatide offers potential complementary effects that improve glycaemic control and facilitate weight loss.
Clinical trials (SURPASS and SURMOUNT programmes) have demonstrated that Mounjaro can reduce HbA1c levels substantially in people with type 2 diabetes, whilst also producing significant reductions in body weight—with higher doses achieving 15% or more weight loss in some study populations. Common adverse effects include gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and constipation, which are typically mild to moderate and tend to diminish over time.
Important safety considerations include reports of acute pancreatitis (patients should be advised to seek medical attention for severe abdominal pain), potential risk of hypoglycaemia when used with insulin or sulfonylureas (dose adjustments may be needed), gallbladder disease, and risk of dehydration from gastrointestinal effects. Animal studies have shown thyroid C-cell tumours, though the relevance to humans is unknown. Mounjaro is available on NHS prescription under specific criteria aligned with NICE guidance (TA870 for type 2 diabetes and TA906 for weight management), and patients should be monitored regularly by their healthcare team.
Suspected adverse reactions should be reported via the MHRA Yellow Card scheme.
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Cortisol is a steroid hormone produced by the adrenal glands, which sit atop each kidney. Often referred to as the body's primary stress hormone, cortisol plays a vital role in numerous physiological processes, including the regulation of metabolism, immune function, blood pressure, and the body's response to stress. Cortisol secretion follows a natural circadian rhythm, with levels typically peaking in the early morning to help us wake and gradually declining throughout the day.
When the body perceives stress—whether physical, emotional, or metabolic—the hypothalamic-pituitary-adrenal (HPA) axis is activated, triggering the release of cortisol. In the short term, this response is adaptive, mobilising energy stores, increasing alertness, and modulating inflammation. However, chronic elevation of cortisol can have detrimental effects, contributing to weight gain (particularly central adiposity), insulin resistance, hypertension, mood disturbances, and impaired immune function.
Conversely, insufficient cortisol production (as seen in adrenal insufficiency or Addison's disease) can lead to fatigue, low blood pressure, hypoglycaemia, and potentially life-threatening adrenal crisis. Signs of adrenal crisis include severe weakness, vomiting, confusion, and hypotension, requiring immediate medical attention. Patients with known adrenal insufficiency should carry a steroid emergency card and emergency medication.
Cortisol levels are influenced by a multitude of factors, including chronic stress, sleep deprivation, obesity, metabolic syndrome, certain medications (such as corticosteroids), and underlying endocrine disorders like Cushing's syndrome, where cortisol is excessively produced.
Measuring cortisol can be complex, as levels fluctuate throughout the day. Tests may include early morning serum cortisol, 24-hour urinary free cortisol, late-night salivary cortisol, or dynamic tests such as the dexamethasone suppression test and short Synacthen (ACTH stimulation) test for suspected adrenal insufficiency. Results can be affected by exogenous glucocorticoids, oestrogen therapy, anticonvulsants, and shift work, requiring careful interpretation in the clinical context.
There is a well-established bidirectional relationship between obesity, metabolic dysfunction, and cortisol dysregulation. Individuals with obesity, particularly those with central (abdominal) fat distribution, often exhibit alterations in cortisol metabolism. Whilst total circulating cortisol levels may be normal or only modestly elevated, there is evidence of increased cortisol production and turnover, as well as enhanced local cortisol generation in adipose tissue via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).
Chronic stress and elevated cortisol can promote weight gain through several mechanisms: increasing appetite (particularly for high-calorie, palatable foods), promoting visceral fat deposition, impairing insulin sensitivity, and disrupting sleep patterns. This creates a vicious cycle, as excess adiposity and insulin resistance can further dysregulate the HPA axis, perpetuating metabolic disturbance.
Weight loss, achieved through lifestyle modification, pharmacotherapy, or bariatric surgery, has been shown to improve cortisol regulation in some individuals. Studies suggest that significant weight reduction can improve aspects of HPA axis function, reduce visceral adiposity, and improve insulin sensitivity—all of which may contribute to more balanced cortisol dynamics. However, the relationship is complex and responses vary considerably between individuals.
It is important to note that whilst metabolic improvements associated with weight loss may indirectly influence cortisol regulation, weight loss medications are not designed or licensed to treat cortisol disorders. Conditions such as Cushing's syndrome require specific investigation and targeted treatment. Patients concerned about cortisol-related symptoms should seek medical evaluation rather than assuming weight loss alone will resolve underlying endocrine pathology.
NICE guidance (CG189) on obesity management emphasises a multifaceted approach, with pharmacotherapy as one component alongside dietary, physical activity, and behavioural interventions.
Currently, there is no official evidence or established clinical link indicating that Mounjaro (tirzepatide) directly lowers cortisol levels or is intended for the treatment of cortisol-related disorders. The primary hormonal targets of tirzepatide are the GIP and GLP-1 receptors, which influence glucose homeostasis, insulin secretion, and appetite regulation. The drug's effects on other hormonal systems, including the HPA axis and cortisol production, have not been a primary focus of clinical trials to date.
That said, emerging research into GLP-1 receptor agonists (a related class of medications) has explored potential indirect effects on stress and metabolic hormones. Some preclinical studies have suggested that GLP-1 signalling may interact with stress response pathways, though findings remain preliminary and require further investigation in well-designed human studies.
Any effects on cortisol regulation would likely be indirect, mediated through improvements in metabolic health, weight loss, insulin sensitivity, and inflammation rather than direct cortisol suppression. The UK product information for Mounjaro makes no claims regarding effects on cortisol levels or stress-related conditions.
Given that Mounjaro facilitates substantial weight loss and improves metabolic parameters in individuals with type 2 diabetes and obesity—conditions often associated with cortisol dysregulation—it is plausible that patients may experience secondary improvements in HPA axis function as their overall metabolic health improves. However, this would be a consequence of the drug's primary actions rather than a direct pharmacological effect on cortisol synthesis or secretion.
Patients should not use Mounjaro with the expectation of treating elevated cortisol or stress-related hormonal imbalances. If cortisol abnormalities are suspected, appropriate endocrine investigation is essential. Mounjaro is prescribed for licensed indications under specialist or primary care supervision, and its use should align with NICE-approved pathways for diabetes (TA870) and weight management (TA906).
If you are concerned about abnormal cortisol levels—whether elevated or deficient—it is essential to consult your GP or an endocrinologist for proper assessment. Symptoms of high cortisol (Cushing's syndrome) may include:
Unexplained weight gain, particularly around the abdomen and face
Purple striae (stretch marks) on the skin
Easy bruising and thinning skin
Muscle weakness
High blood pressure and elevated blood glucose
Mood changes, including anxiety and depression
Symptoms of low cortisol (adrenal insufficiency) may include persistent fatigue, weight loss, low blood pressure, dizziness, and hypoglycaemia. Both conditions require specific diagnostic testing, such as blood and urine cortisol measurements, dynamic endocrine function tests, and imaging studies where appropriate.
In UK practice, initial screening for Cushing's syndrome typically includes 24-hour urinary free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test. For suspected adrenal insufficiency, early morning cortisol and short Synacthen (ACTH stimulation) tests are standard. Abnormal results should prompt referral to specialist endocrine services for confirmation and identification of the underlying cause.
Treatment for Cushing's syndrome is tailored to the aetiology (pituitary adenoma, adrenal tumour, ectopic ACTH production, or exogenous corticosteroid use) and may include surgery, radiotherapy, or medical therapy with cortisol-lowering agents. Adrenal insufficiency requires lifelong hormone replacement therapy with careful monitoring and emergency protocols for illness or stress.
For individuals with stress-related cortisol dysregulation without overt pathology, management focuses on lifestyle interventions: stress reduction techniques (such as cognitive behavioural therapy, mindfulness, and relaxation exercises), regular physical activity, adequate sleep, and a balanced diet. Weight management, where appropriate, can also support metabolic and hormonal health.
Mounjaro is not a treatment for cortisol disorders, and patients should not delay seeking appropriate medical evaluation if they have concerns about their cortisol levels. Always discuss any new or worsening symptoms with your healthcare provider to ensure timely and accurate diagnosis. The NHS website and Society for Endocrinology provide patient resources on adrenal disorders that may be helpful for further information.
No, Mounjaro is not licensed or intended for treating cortisol disorders such as Cushing's syndrome. It is prescribed for type 2 diabetes and weight management, and any effects on cortisol would be indirect through metabolic improvements rather than direct hormonal action.
Significant weight loss can improve aspects of HPA axis function, reduce visceral adiposity, and enhance insulin sensitivity, which may contribute to more balanced cortisol dynamics. However, responses vary between individuals and weight loss alone does not treat underlying cortisol disorders.
Consult your GP or an endocrinologist for proper assessment through specific diagnostic tests such as blood and urine cortisol measurements or dynamic endocrine function tests. Do not delay seeking medical evaluation if you have symptoms of cortisol abnormalities.
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DisclaimerThis content is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional with any medical questions or concerns. Use of the information is at your own risk, and we are not responsible for any consequences resulting from its use.
