Mounjaro (tirzepatide) is a dual GIP and GLP-1 receptor agonist licensed in the UK for treating type 2 diabetes mellitus in adults. Many patients wonder whether Mounjaro causes ketosis, particularly given the substantial weight loss and reduced appetite commonly experienced during treatment. Whilst Mounjaro does not directly induce ketosis through its pharmacological mechanism, the significant caloric restriction it promotes can lead to mild nutritional ketosis in some individuals. This article examines the relationship between Mounjaro and ketosis, distinguishes nutritional ketosis from diabetic ketoacidosis, and provides essential safety guidance for patients and healthcare professionals.

Understanding Mounjaro and Its Mechanism of Action

Mounjaro (tirzepatide) is a novel glucose-lowering medication licensed in the UK for the treatment of type 2 diabetes mellitus in adults. It represents a significant advancement in diabetes pharmacotherapy as the first dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist available for clinical use.

The medication works through a sophisticated dual mechanism. By activating GIP receptors, Mounjaro enhances insulin secretion from pancreatic beta cells in a glucose-dependent manner, meaning insulin release only occurs when blood glucose levels are elevated. Simultaneously, GLP-1 receptor activation suppresses glucagon secretion from pancreatic alpha cells, slows gastric emptying, and promotes satiety through central nervous system pathways. This combined action results in improved glycaemic control and substantial weight reduction in many patients.

Key pharmacological effects include:

• Enhanced glucose-dependent insulin secretion

• Reduced inappropriate glucagon release

• Delayed gastric emptying, leading to prolonged satiety

• Reduced appetite and caloric intake

• Improved insulin sensitivity, primarily through weight loss effects

Mounjaro is administered once weekly via subcutaneous injection. The recommended starting dose is 2.5 mg once weekly for 4 weeks, then increased in 2.5 mg increments at minimum 4-week intervals to a maximum of 15 mg, based on individual response and tolerability. The MHRA approved tirzepatide following clinical trials demonstrating superior glycaemic control and weight loss compared to other GLP-1 receptor agonists.

While Mounjaro's glucose-dependent mechanism reduces the risk of hypoglycaemia when used as monotherapy or with metformin, this risk increases significantly when combined with insulin or sulfonylureas. Dose reduction of these medications may be required when starting tirzepatide to minimise hypoglycaemia risk.

Does Mounjaro Cause Ketosis?

Mounjaro does not directly cause physiological ketosis in the manner associated with very low-carbohydrate diets or fasting states. However, the substantial weight loss and reduced caloric intake that many patients experience whilst taking tirzepatide can lead to mild nutritional ketosis in some individuals. This represents a normal metabolic adaptation rather than a pathological process.

Nutritional ketosis occurs when the body shifts towards using fat as its primary fuel source due to reduced carbohydrate availability or caloric restriction. As Mounjaro significantly suppresses appetite and delays gastric emptying, patients often consume considerably fewer calories and carbohydrates than previously. This metabolic shift can result in the production of ketone bodies (beta-hydroxybutyrate, acetoacetate, and acetone) as the liver breaks down fatty acids for energy.

Important distinctions to understand:

• Nutritional ketosis is generally mild, with blood ketone levels typically below 3 mmol/L, and is not harmful in individuals without diabetes complications

• This differs fundamentally from diabetic ketoacidosis (DKA), a serious medical emergency characterised by very high ketone levels, severe hyperglycaemia, and metabolic acidosis

• Mounjaro improves glycaemic control but does not eliminate DKA risk; vigilance is needed during illness, fasting, or with concomitant insulin or SGLT2 inhibitor use

Patients taking both Mounjaro and SGLT2 inhibitors should be particularly cautious and check ketones when unwell even if blood glucose is not elevated, as this combination may increase the risk of euglycaemic ketoacidosis. During illness, patients should follow UK sick-day rules: maintain hydration, continue basal insulin if prescribed, check blood ketones if blood glucose exceeds 13.9 mmol/L or if feeling unwell, and seek medical advice if ketones are elevated or symptoms worsen.

Diabetic Ketoacidosis Risk with Mounjaro

Diabetic ketoacidosis (DKA) is an uncommon but serious complication in type 2 diabetes. While the absolute risk with Mounjaro remains very low, cases have been reported with GLP-1 receptor agonists, particularly when insulin is rapidly reduced or discontinued upon starting treatment. DKA occurs when severe insulin deficiency leads to uncontrolled lipolysis, excessive ketone production, hyperglycaemia, and metabolic acidosis.

In type 2 diabetes, DKA risk with Mounjaro is extremely low because these patients typically retain some endogenous insulin production. However, certain clinical scenarios may increase vulnerability. Patients with latent autoimmune diabetes in adults (LADA), those with significantly impaired beta-cell function, or individuals experiencing acute physiological stress (such as severe infection, surgery, or acute illness) may theoretically be at higher risk. Additionally, euglycaemic DKA—where ketoacidosis develops without marked hyperglycaemia—is uncommon but most frequently associated with SGLT2 inhibitors rather than GLP-1 receptor agonists. Extra vigilance is warranted if these medications are used in combination.

Risk factors that warrant particular caution include:

• Severe intercurrent illness or major surgery

• Significant reduction or cessation of insulin therapy

• Prolonged fasting or very low carbohydrate intake

• Excessive alcohol consumption

• Undiagnosed type 1 diabetes or LADA

• Concomitant use of SGLT2 inhibitors

The MHRA and EMA product information for Mounjaro does not list DKA as a common adverse effect, and large clinical trials have not demonstrated an increased incidence compared to placebo or active comparators. Healthcare professionals should ensure Mounjaro is prescribed only for confirmed type 2 diabetes and not for patients with type 1 diabetes, where DKA risk would be substantially elevated.

Recognising Symptoms of Ketoacidosis

Early recognition of diabetic ketoacidosis is crucial for prompt treatment and prevention of serious complications. Whilst DKA is rare with Mounjaro use in type 2 diabetes, patients and healthcare professionals should remain vigilant for warning signs, particularly during intercurrent illness or other physiological stress.

DKA typically develops over hours to days and presents with a constellation of symptoms reflecting metabolic decompensation. Classical features include persistent hyperglycaemia (though euglycaemic DKA can occur), excessive thirst (polydipsia), and increased urination (polyuria) as the body attempts to excrete excess glucose and ketones. As acidosis develops, patients experience nausea, vomiting, and abdominal pain, which may be mistaken for gastroenteritis or other gastrointestinal conditions.

Key symptoms requiring immediate medical attention:

• Persistent nausea and vomiting lasting more than a few hours

• Severe abdominal pain

• Unusual fatigue or weakness

• Rapid, deep breathing (Kussmaul respiration)

• Fruity-smelling breath (acetone odour)

• Confusion or altered consciousness

• Blood glucose levels persistently above 13.9 mmol/L (though may be lower in euglycaemic DKA)

Patients using Mounjaro should be educated about these warning signs during initiation and at regular review appointments. Those with home blood glucose monitoring capabilities should test more frequently during illness and check blood ketones if glucose exceeds 13.9 mmol/L or if feeling unwell. Blood ketone levels of ≥1.5 mmol/L require urgent medical advice, while levels ≥3.0 mmol/L or symptoms suggestive of DKA warrant immediate medical assessment.

Patients taking SGLT2 inhibitors alongside Mounjaro should check ketones if unwell even with normal glucose levels and follow sick-day rules carefully, as this combination increases the risk of euglycaemic ketoacidosis.

Safety Considerations and When to Seek Medical Advice

Safe use of Mounjaro requires appropriate patient selection, education, and ongoing monitoring. Healthcare professionals should conduct thorough baseline assessments before prescribing tirzepatide, including confirmation of type 2 diabetes diagnosis and renal function testing. According to the UK Summary of Product Characteristics (SmPC), hypersensitivity to the active substance or excipients is the only formal contraindication.

Patients should receive comprehensive counselling about common adverse effects, which predominantly involve gastrointestinal symptoms including nausea, vomiting, diarrhoea, and constipation. These effects are typically mild to moderate and diminish over time, but can occasionally lead to dehydration if not managed appropriately. Adequate hydration is particularly important, especially during dose escalation or intercurrent illness.

The SmPC recommends gradual dose titration to minimise gastrointestinal side effects: starting with 2.5 mg once weekly for 4 weeks, then increasing in 2.5 mg increments at minimum 4-week intervals to a maximum of 15 mg based on response and tolerability. When Mounjaro is used with insulin or sulfonylureas, dose reduction of these medications should be considered to minimise hypoglycaemia risk.

Patients should contact their GP or healthcare provider if they experience:

• Persistent vomiting preventing adequate fluid or food intake

• Severe or persistent abdominal pain (potential pancreatitis)

• Signs of dehydration (dark urine, dizziness, reduced urine output)

• Unexplained weight loss exceeding expected therapeutic effects

• Any symptoms suggestive of ketoacidosis as previously described

Immediate medical attention (A&E or 999) is warranted for:

• Severe abdominal pain with vomiting

• Confusion or reduced consciousness

• Rapid breathing with fruity breath odour

• Blood ketone levels ≥3.0 mmol/L

• Inability to keep down fluids for more than 12 hours

Patients planning surgery should discuss Mounjaro with their surgical/anaesthetic team, as some centres may advise withholding weekly GLP-1 receptor agonists pre-procedure due to delayed gastric emptying effects. During acute illness, patients should maintain hydration and follow sick-day rules.

Regular follow-up appointments should monitor glycaemic control (HbA1c), weight, renal function, and treatment tolerability. Patients should be encouraged to maintain a balanced diet despite reduced appetite and to stay well hydrated. Patients are advised to report any suspected side effects via the MHRA Yellow Card scheme.

Frequently Asked Questions