Tirzepatide
Tirzepatide is a once-weekly subcutaneous peptide that activates both the GIP and GLP-1 receptors. It is approved in adults with type 2 diabetes and, under a separate brand, for chronic weight management.
- Chemical formula
- C225H348N48O68
- CAS number
- 2023788-19-2
- ATC code
- A10BX16
- Molecular weight
- 4813.5 g/mol
- Drug class
- GIP/GLP-1 dual receptor agonist
- Also known as
- LY3298176, Tirzepatida
What is it?
Tirzepatide is a synthetic 39-amino-acid peptide modified with a fatty diacid that allows reversible albumin binding and weekly subcutaneous dosing. Unlike single-pathway GLP-1 receptor agonists, it acts simultaneously on the glucose-dependent insulinotropic polypeptide (GIP) receptor and the GLP-1 receptor, both of which contribute to incretin physiology. It was developed by Eli Lilly and approved in 2022 for type 2 diabetes; a second brand name received approval for chronic weight management in adults with obesity or with overweight and weight-related comorbidities.
Mechanism of action
Tirzepatide binds with high affinity to the GIP receptor and to the GLP-1 receptor. Activation of both incretin pathways enhances glucose-dependent insulin secretion, suppresses inappropriate glucagon release, slows gastric emptying and reduces appetite through hypothalamic centres. The dual mechanism is thought to underlie the larger glycaemic and weight reductions reported in randomised trials compared with selective GLP-1 receptor agonists. Hypoglycaemia is rare in monotherapy because insulin secretion is stimulated only when glucose is elevated.
Pharmacokinetics
After subcutaneous administration, peak plasma concentrations are reached after approximately 8 to 72 hours. Albumin binding is greater than 99%. The terminal half-life is about five days, supporting weekly dosing with a steady state reached after roughly four weeks. Metabolism occurs through proteolytic cleavage by ubiquitous peptidases and beta-oxidation of the fatty diacid moiety; metabolites are eliminated mainly in urine and faeces. No clinically relevant interactions through cytochrome P450 enzymes have been reported.
Indications
Tirzepatide is approved in adults with type 2 diabetes mellitus, as monotherapy or in combination with other antidiabetic agents, to improve glycaemic control. Under a separate brand name, the same molecule is approved for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with obesity, or with overweight and at least one weight-related comorbidity. According to the prescribing information, treatment must be initiated and supervised by a qualified clinician.
Safety profile
The most common adverse effects are gastrointestinal: nausea, diarrhoea, vomiting, decreased appetite, constipation and abdominal discomfort, generally mild to moderate and most pronounced during dose escalation. Acute pancreatitis, gallbladder disease and injection-site reactions have been reported. Hypoglycaemia may occur in combination with insulin or sulfonylureas. The product carries a boxed warning regarding thyroid C-cell tumours observed in rodents; medullary thyroid carcinoma and multiple endocrine neoplasia type 2 are contraindications, as is severe gastroparesis.
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Frequently asked questions
How is tirzepatide different from semaglutide? ▾
Both are once-weekly subcutaneous peptides that act on the GLP-1 receptor, but tirzepatide also activates the GIP receptor, giving it a dual incretin mechanism. Randomised clinical trials suggest larger reductions in glycated haemoglobin and body weight at the highest doses of tirzepatide compared with semaglutide, although gastrointestinal tolerability is broadly similar. The choice between them is made by the prescriber based on glycaemic and metabolic targets and individual response.
How is tirzepatide dosed? ▾
Tirzepatide is administered once weekly by subcutaneous injection in the abdomen, thigh or upper arm. According to the prescribing information, treatment starts at 2.5mg per week as a tolerability dose, with stepwise increases every four weeks to a maintenance dose of 5, 10 or 15mg, selected by the prescriber. The dose escalation schedule is designed to limit early gastrointestinal adverse effects. The injection day can be changed if the new day is at least three days from the previous one.
Does tirzepatide require refrigeration? ▾
Yes. According to the prescribing information, unused pens are stored in a refrigerator between 2°C and 8°C. After first use or during travel, the pen can be kept at room temperature below 30°C for a limited period defined in the leaflet, after which it should be discarded. Freezing damages the peptide. Cold-chain integrity is one reason regulatory agencies caution against purchasing GLP-1 or dual incretin agonists from unverified online sources.
Can tirzepatide be used by people without diabetes? ▾
Yes, in selected indications. Under a separate brand name, tirzepatide is approved for chronic weight management in adults with obesity or with overweight and at least one weight-related comorbidity. It is not approved as a cosmetic weight-loss agent and should be prescribed only after a full medical assessment. According to the prescribing information, lifestyle measures such as diet and physical activity must accompany pharmacological treatment.
What are the main contraindications for tirzepatide? ▾
Personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2 and known hypersensitivity to tirzepatide are formal contraindications. Caution is required in patients with previous pancreatitis, severe gastroparesis, diabetic retinopathy or active gallbladder disease, and during pregnancy and breastfeeding. According to the prescribing information, the medical history and current medication list must be reviewed by a clinician before any prescription.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.