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Tirzepatide – Mechanism, Dosage & Uses

Tirzepatide is a modern medication for treating type 2 diabetes and obesity. As a dual GIP and GLP-1 receptor agonist, it lowers blood sugar and significantly reduces body weight.

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Things worth knowing about "Tirzepatide"

Tirzepatide is a modern medication for treating type 2 diabetes and obesity. As a dual GIP and GLP-1 receptor agonist, it lowers blood sugar and significantly reduces body weight.

What is Tirzepatide?

Tirzepatide is an innovative active ingredient belonging to the class of dual incretin receptor agonists. It simultaneously activates two receptors in the body: the GIP receptor (glucose-dependent insulinotropic polypeptide) and the GLP-1 receptor (glucagon-like peptide-1). This dual mechanism of action enables tirzepatide to effectively lower blood sugar levels while also significantly reducing body weight. The medication is administered once weekly as a subcutaneous injection and is marketed under the brand name Mounjaro.

Indications

Tirzepatide is approved for:

Type 2 diabetes mellitus: To improve glycaemic control in adults, as an adjunct to diet and exercise.
Chronic overweight and obesity: For long-term weight management in adults with a body mass index (BMI) of 30 kg/m² or greater, or from a BMI of 27 kg/m² in the presence of at least one weight-related comorbidity.

Mechanism of Action

Tirzepatide mimics the natural incretin hormones GIP and GLP-1, which are released from the gut after a meal. The dual mechanism of action includes the following effects:

Stimulation of insulin secretion: Insulin release from the pancreas is stimulated in a glucose-dependent manner.
Inhibition of glucagon secretion: The release of glucagon, a blood-sugar-raising hormone, is reduced.
Slowing of gastric emptying: Food is digested more slowly, leading to a prolonged feeling of fullness.
Appetite reduction: Tirzepatide acts on brain centres that regulate hunger, resulting in reduced food intake.
Improvement of insulin sensitivity: Body tissues respond better to insulin, improving glucose utilisation.

Dosage and Administration

Tirzepatide is administered once weekly as a subcutaneous injection (under the skin). Typical injection sites include the abdomen, thigh, or upper arm. Treatment generally starts at a low dose of 2.5 mg per week, which is gradually escalated to improve tolerability. Recommended maintenance doses range from 5 mg to 15 mg weekly, depending on therapeutic response and tolerability.

Side Effects

Like all medications, tirzepatide can cause side effects. The most common include:

Gastrointestinal complaints: Nausea, vomiting, diarrhoea, and constipation, especially at the start of therapy or when the dose is increased.
Loss of appetite
Injection site reactions: Redness, swelling, or itching.
Hypoglycaemia (low blood sugar): Particularly when used in combination with insulin or sulphonylureas.
Heart palpitations (tachycardia)

Rare but serious side effects include inflammation of the pancreas (pancreatitis) and possible changes to the retina of the eye. Patients with a personal or family history of medullary thyroid carcinoma should not use tirzepatide.

Contraindications and Precautions

Tirzepatide must not be used in:

Patients with known hypersensitivity to the active ingredient.
Patients with type 1 diabetes mellitus.
Pregnancy and breastfeeding (due to insufficient safety data).
Patients with severe renal impairment (use with caution).

Clinical Evidence

Tirzepatide was extensively studied in the SURPASS clinical trial programme (for type 2 diabetes) and the SURMOUNT programme (for obesity). Results demonstrated outstanding reductions in HbA1c levels and significant weight loss of up to 22.5% of body weight in the highest dose group – results previously not achieved with any comparable medication.

References

European Medicines Agency (EMA): Mounjaro (Tirzepatide) - Summary of Product Characteristics. EMA, 2023. Available at: www.ema.europa.eu
Frías JP et al. - Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 2021; 385:503-515.
Jastreboff AM et al. - Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 2022; 387:205-216.

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