The following information must be referred to when considering prescribing tirzepatide (Mounjaro) to a service user. This document should be considered alongside the 'General Prescribing Policy' and any NICE guideline and current clinical research or guidance.
What is Mounjaro
Mounjaro is a medicine for weight loss and weight maintenance that contains the active substance tirzepatide. Tirzepatide is a long-acting dual GIP and GLP-1 receptor agonist. Both receptors are present in the pancreatic α and β endocrine cells, heart, vasculature, immune cells (leukocytes), gut, and kidney. GIP receptors are also present in adipocytes.
In addition, both GIP and GLP-1 receptors are expressed in the areas of the brain important to appetite regulation. Tirzepatide is highly selective to human GIP and GLP-1 receptors. Tirzepatide has a high affinity to both the GIP and GLP-1 receptors. The activity of tirzepatide on the GIP receptor is similar to the native GIP hormone. The activity of tirzepatide on the GLP-1 receptor is lower compared to the native GLP-1 hormone.
Mounjaro works by acting on receptors in the brain that control your appetite, causing you to feel fuller and less hungry and experience less craving for food. This will help you eat less food and reduce your body weight. Mounjaro should be used with a reduced-calorie meal plan and increased physical activity.
Inclusion Criteria
Mounjaro is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with an initial Body Mass Index (BMI) of:
- ≥ 30 kg/m2 (obesity), or
- ≥ 27 kg/m2 to <30 kg/m2 (overweight) in the presence of at least one weight-related comorbidity such as dysglycaemia (pre-diabetes or type 2 diabetes mellitus), hypertension, dyslipidemia or obstructive sleep apnoea
- Consent to treatment and adherence to appropriate dietary intake
- Age 18-75 years
- If patients have been unable to lose at least 5% of their initial body weight after 6 months of treatment, a decision is required on whether to continue treatment, taking into account the benefit/risk profile in the individual patient.
Dosage schedule
The starting dose of tirzepatide is 2.5 mg once weekly. After 4 weeks, the dose should be increased to 5 mg once weekly. If needed, dose increases can be made in 2.5 mg increments after a minimum of 4 weeks on the current dose.
The recommended maintenance doses are 5, 10 and 15 mg.
The maximum dose is 15 mg once weekly
Method of administration
Mounjaro is administered once weekly at any time of the day, with or without meals.
It is to be injected subcutaneously in the abdomen, in the thigh or in the upper arm. The injection site can be changed. It should not be administered intravenously or intramuscularly.
The day of weekly administration can be changed if necessary as long as the time between two doses is at least 3 days (>72 hours). After selecting a new dosing day, once-weekly dosing should be continued.
Patients should be advised to read the instructions for use included in the package leaflet carefully before administering the medicinal product.
Red flags, exclusion and/or referral criterion:
Individuals with a BMI less than 30Kg/ m2or below 27 kg/ m2with additional risk factors such as type 2 diabetes, hypertension, or hypercholesterolemia.
- Pregnancy or Breast-feeding
- Individuals with renal and/or hepatic conditions/impairment
- Allergy to any GLP-1 receptor (Exenatide, Lixisenatide,Dulaglutide,tirzepatide,liraglutide)
- History of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Prior serious hypersensitivity reaction to liraglutide or to any of the product components
- Type 1 diabetes or insulin-dependent diabetes
- Depressive thoughts with suicidal ideations
- Personal or family history of thyroid cancer
- Previous episode of pancreatitis
- History of gallstones
- History of eating disorders
- Alcoholism
- Hypertriglyceridemia
- Hepatic or Renal dysfunction
- Gastroparesis
- Age under 18 years or over 75 years
Patient counseling:
- Liraglutide must be taken with the recommended healthy balanced diet containing less than a regular exercise routine.
- Watch our online video to learn proper injection techniques
- tirzepatide should be injected at the same time every week and can be injected before or after food
- The dosage for this medication needs to be tapered up in order to avoid any gastro-intestinal side effects. Doses should be maintained for 1 week before being increased by 0.6mg every week until a dose of 3mg/day is reached. After that, the dose should be maintained at 3mg/day
- Injections should be issued in the upper thigh, upper arm, or abdomen around the umbilical region and rotate injection sites.
- If a dose is missed, it should be administered as soon as possible and within 5 days after the missed dose. If more than 5 days have passed, the missed dose should be skipped, and the next dose should be administered on the regularly scheduled day. In each case, patients can then resume their regular once-weekly dosing schedule. If more doses are missed, reducing the starting dose for re-initiation should be considered
- The day of weekly administration can be changed if necessary as long as the time between two doses is at least 3 days (>72 hours). After selecting a new dosing day, once-weekly dosing should be continued.
Special warnings and precautions for use
Gastrointestinal effects
The use of GIP/GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions that can cause dehydration, which in rare cases can lead to a deterioration of renal function. Patients should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion.
Acute pancreatitis
Acute pancreatitis has been observed with the use of GIP/GLP-1 receptor agonists. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, tirzepatide should be discontinued; if confirmed, tirzepatide should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
In the absence of other signs and symptoms of acute pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis.
For patients with diabetes
Tirzepatide must not be used as a substitute for insulin in patients with diabetes.
Hypoglycaemia in patients with diabetes
Insulin and sulfonylurea are known to cause hypoglycaemia. Patients treated with tirzepatide in combination with a sulfonylurea or insulin may have an increased risk of hypoglycaemia. The risk of hypoglycaemia can be lowered by reducing the dose of sulfonylurea or insulin when initiating treatment with a GIP/GLP-1 receptor agonist. The addition of tirzepatide 2.4 mg in patients treated with insulin has not been evaluated.
Diabetic retinopathy in patients with type 2 diabetes
In patients with diabetic retinopathy treated with insulin and, an increased risk of developing diabetic retinopathy complications has been observed. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, but other mechanisms cannot be excluded. Patients with diabetic retinopathy using tirzepatide should be monitored closely and treated according to clinical guidelines. There is no experience with tirzepatide 2.4 mg in patients with type 2 diabetes with uncontrolled or potentially unstable diabetic retinopathy.
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 'sodium-free'.
Interaction with other medicinal products and other forms of interaction
As with other GIP/GLP-1 receptor agonists, tirzepatide may delay gastric emptying and could potentially influence the absorption of concomitantly administered oral medicinal products. No clinically relevant effect on the rate of gastric emptying was observed with tirzepatide 2.4 mg. In clinical pharmacology trials assessing the effect of tirzepatide 1.0 mg on the absorption of co-administered oral medications at steady state, no clinically relevant drug-drug interactions with tirzepatide were observed based on the evaluated medications. Therefore, no dose adjustment is required when co-administered with tirzepatide.
Oral contraceptives
Tirzepatide is not anticipated to decrease the effectiveness of oral contraceptives as tirzepatide did not change the overall exposure of ethinylestradiol and levonorgestrel to a clinically relevant degree when an oral contraceptive combination medicinal product (0.03 mg ethinylestradiol/0.15 mg levonorgestrel) was co-administered with tirzepatide. Exposure to ethinylestradiol was not affected; an increase of 20% was observed for levonorgestrel exposure at a steady state. Cmax was not affected by any of the compounds.
