Tirzepatide

Tirzepatide is a long-acting injectable medicine belonging to the class of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. It activates both hormone receptors, which are involved in regulating blood glucose, appetite and energy balance. In people with type 2 diabetes, tirzepatide enhances insulin secretion when blood glucose is elevated, reduces glucagon secretion in a glucose-dependent manner and helps improve glycaemic control. It also delays gastric emptying, particularly during initial treatment, and acts on appetite-regulating pathways to reduce food intake and support weight reduction. These combined effects make it useful in diabetes management and, where approved, long-term weight management.

Tirzepatide is administered by subcutaneous injection, generally once weekly. Depending on the country and authorised product indication, it may be prescribed to improve blood glucose control in type 2 diabetes, reduce excess body weight in eligible adults, or treat certain weight-related conditions. It is used alongside appropriate dietary changes and physical activity rather than as a substitute for comprehensive care. Common adverse effects mainly involve the gastrointestinal system, while important risks include pancreatitis, gallbladder disease, dehydration-related kidney injury and hypoglycaemia when combined with certain diabetes medicines. Treatment requires individualised dose escalation and clinical supervision.

Tirzepatide was developed by Eli Lilly and Company as a synthetic peptide designed to activate both GIP and GLP-1 receptors. Its development built on research into incretin hormones and their roles in glucose regulation, appetite and metabolism. The United States Food and Drug Administration (FDA) approved Mounjaro for type 2 diabetes on 13 May 2022. The European Commission granted marketing authorisation for Mounjaro on 15 September 2022. In the United States, tirzepatide was subsequently approved under the product name Zepbound for chronic weight management in November 2023 and for moderate-to-severe obstructive sleep apnoea in adults with obesity in December 2024. Indications have continued to evolve as additional evidence has become available. The SURPASS phase III clinical trial programme evaluated its effectiveness and safety in type 2 diabetes, while the SURMOUNT programme investigated weight management. Regulatory approvals and authorised indications vary by country and product, so the applicable local prescribing information should be checked before treatment.

Tirzepatide is used to improve blood glucose control in people with type 2 diabetes, alongside diet and physical activity. Depending on local approval, it may be prescribed alone when appropriate or in combination with other glucose-lowering medicines. In eligible adults with obesity, or overweight accompanied by weight-related health conditions, it may be used with a reduced-calorie diet and increased physical activity for long-term weight management. In the United States, tirzepatide is also approved under the Zepbound indication for moderate-to-severe obstructive sleep apnoea in adults with obesity. The appropriate indication depends on the patient's diagnosis, weight-related health risks, treatment history and the locally approved product information. Tirzepatide is not intended for type 1 diabetes or the treatment of diabetic ketoacidosis. It should not routinely be combined with another tirzepatide-containing product or a GLP-1 receptor agonist.

Tirzepatide is administered by subcutaneous injection once weekly, generally in the abdomen, thigh or upper arm. For adults receiving the US-approved diabetes or weight-management regimens, treatment usually begins at 2.5 mg once weekly for four weeks, followed by an increase to 5 mg once weekly. If needed and tolerated, the dose may be increased in 2.5 mg increments after at least four weeks at the current dose. The maximum approved dose is 15 mg once weekly for adults under the relevant US indications, although recommended maintenance doses differ according to the indication and product. The initial dose is intended to help the body adjust and is not a maintenance dose. Treatment may continue long term when beneficial and tolerated, with periodic clinical review. Patients should follow the instructions for their specific pen or presentation, rotate injection sites and avoid sharing injection devices. Dose selection and adjustment require clinical supervision, particularly when tirzepatide is used with insulin or sulfonylureas.

Common side effects of tirzepatide include nausea, diarrhoea, vomiting, constipation, abdominal discomfort, reduced appetite and indigestion. These effects are often more noticeable when treatment begins or the dose is increased and may lessen over time. Some patients may experience injection-site reactions, belching or reflux symptoms. Reduced food intake, vomiting or diarrhoea can contribute to dehydration, particularly in older adults or people with impaired kidney function. The likelihood and severity of side effects vary with the dose, treatment combination and individual health status. Smaller meals and appropriate fluid intake may help some patients manage gastrointestinal symptoms, but persistent or severe symptoms require medical assessment. Patients should not increase the dose more quickly than prescribed or discontinue other diabetes medicines without consulting their healthcare professional.

Important risks associated with tirzepatide include acute pancreatitis, gallbladder disease, severe gastrointestinal reactions, dehydration-related acute kidney injury and serious hypersensitivity reactions. Hypoglycaemia can occur, particularly when tirzepatide is used with insulin or sulfonylureas. The US prescribing information contains a boxed warning about thyroid C-cell tumours observed in rodents; the relevance to humans remains uncertain. Under US prescribing information, tirzepatide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Tirzepatide is not recommended in patients with severe gastroparesis under the US product information. Patients should seek prompt medical assessment for persistent severe abdominal pain, repeated vomiting, allergic reactions or symptoms of significant hypoglycaemia. Clinicians may need to withhold or discontinue treatment when serious adverse reactions occur. Patients undergoing general anaesthesia or deep sedation should inform their healthcare team because delayed gastric emptying may increase the risk of pulmonary aspiration.

Before starting tirzepatide, clinicians should review the patient's diabetes history, current medicines, gastrointestinal conditions, kidney function where clinically indicated, history of pancreatitis or gallbladder disease, and personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Blood glucose and glycated haemoglobin should be assessed in patients treated for diabetes, while weight and relevant metabolic measures should be reviewed when treatment is prescribed for weight management. The risk of hypoglycaemia may increase when tirzepatide is combined with insulin or sulfonylureas, potentially requiring supervised adjustment of those medicines. Because tirzepatide delays gastric emptying, it may affect the absorption of oral medicines; additional precautions may be needed for medicines requiring close monitoring. Under US prescribing information, people using oral hormonal contraceptives should use a non-oral method or add a barrier method for four weeks after starting treatment and for four weeks after each dose increase. Tirzepatide should not be used for weight reduction during pregnancy; if pregnancy occurs, medical advice should be sought promptly. Breastfeeding decisions should be discussed with a healthcare professional. Patients should disclose all prescription medicines, supplements and other weight-management treatments before starting therapy.

Prescribers should confirm the intended indication and the applicable locally approved product information before initiating tirzepatide. Explain the gradual dose-escalation schedule and assess gastrointestinal tolerability before each increase. For diabetes management, review blood glucose readings and consider hypoglycaemia risk when insulin or sulfonylureas are used concurrently. For weight management, assess weight trends, nutritional intake, hydration and relevant obesity-related conditions over time. Counsel patients on injection technique, storage instructions, missed-dose management and the importance of using each injection device according to its product instructions. Advise patients to report persistent abdominal pain, severe vomiting, symptoms of dehydration, allergic reactions or signs of low blood glucose. Review oral medicines whose absorption could be affected by delayed gastric emptying, and discuss contraceptive precautions where applicable. Before planned anaesthesia or deep sedation, ensure the procedural team knows that the patient is receiving tirzepatide. Treatment should be individualised, with regular review of effectiveness, adverse effects and ongoing clinical need.