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Dual GIP/GLP-1 Receptor Agonist – Effects and Uses

A dual GIP/GLP-1 receptor agonist is a medication that simultaneously mimics two gut hormones and is used to treat type 2 diabetes and obesity.

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Things worth knowing about "Dual GIP/GLP-1 Receptor Agonist"

A dual GIP/GLP-1 receptor agonist is a medication that simultaneously mimics two gut hormones and is used to treat type 2 diabetes and obesity.

What is a Dual GIP/GLP-1 Receptor Agonist?

A dual GIP/GLP-1 receptor agonist is a modern class of medication known as an incretin mimetic. It simultaneously activates the receptors of two naturally occurring gut hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Both hormones are released in the small intestine following a meal and play a central role in blood sugar regulation and the sensation of satiety. The most well-known representative of this drug class is tirzepatide.

Mechanism of Action

Dual GIP/GLP-1 receptor agonists bind to the receptors of both incretin hormones, producing a combined metabolic effect:

GLP-1 receptor activation: Stimulates glucose-dependent insulin secretion, slows gastric emptying, reduces appetite, and suppresses glucagon release.
GIP receptor activation: Further enhances insulin secretion, exerts positive effects on lipid metabolism, and may improve insulin sensitivity in adipose and muscle tissue.

By activating both receptors simultaneously, these agents achieve a broader and more pronounced metabolic effect compared to pure GLP-1 receptor agonists alone.

Indications

Dual GIP/GLP-1 receptor agonists are approved for:

Type 2 diabetes mellitus: To improve glycaemic control in adults, alongside diet and exercise, either as monotherapy or in combination with other antidiabetic agents.
Obesity and overweight: For chronic weight management in adults with a body mass index (BMI) of 30 kg/m² or greater, or from 27 kg/m² in the presence of at least one weight-related comorbidity.

Dosage and Administration

Dual GIP/GLP-1 receptor agonists such as tirzepatide are administered as a subcutaneous injection (under the skin) once weekly. Treatment typically begins at a low starting dose, which is gradually increased to improve tolerability. Injections are usually given in the abdomen, thigh, or upper arm.

Side Effects

The most common side effects involve the gastrointestinal tract and are generally mild to moderate, occurring most frequently at the start of treatment or following dose escalations:

Nausea
Vomiting
Diarrhoea
Constipation
Decreased appetite

Less common side effects include delayed gastric emptying, pancreatitis (inflammation of the pancreas), and gallbladder disorders. Patients with a personal or family history of medullary thyroid carcinoma should not use this class of medication.

Clinical Evidence

In clinical trials, particularly the SURPASS programme for diabetes and the SURMOUNT programme for obesity, tirzepatide demonstrated superior efficacy in reducing blood glucose levels and body weight compared to other antidiabetic agents, including pure GLP-1 receptor agonists. Average weight reductions of up to 20-22% of baseline body weight were observed in clinical studies.

Comparison with GLP-1 Receptor Agonists

Unlike pure GLP-1 receptor agonists (e.g. semaglutide, liraglutide), dual GIP/GLP-1 receptor agonists additionally activate the GIP receptor. This results in more pronounced weight reduction and in some cases improved glycaemic control in clinical studies. The additional GIP component is considered a key contributor to the enhanced efficacy of this drug class.

References

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

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