The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist

Oct 6, 2023Journal of lipid and atherosclerosis

Tirzepatide’s effects on the heart and blood vessels as a dual activator of two blood sugar hormones

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Abstract

Tirzepatide significantly reduces glycated hemoglobin levels and body weight in patients with type 2 diabetes mellitus.

Tirzepatide acts as a dual receptor agonist for the GLP-1 and GIP hormones.
The combination of GLP-1 and GIP is associated with glucose-lowering effects in type 2 diabetes.
Tirzepatide's mechanism may contribute to its potential cardiovascular benefits.
Preclinical and clinical data suggest cardiovascular effects of tirzepatide.

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Glucagon-like peptide-1 (GLP-1) receptor agonists have been used extensively in the clinic and have an established safety profile in cardiovascular disease settings. For the treatment of peptide-secreting enteroendocrine cells, most research has focused on developing peptide multi-agonists as most of these cells are multihormonal. Among the various peptides secreted by enteroendocrine cells, the combination of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) is an attractive strategy for treating type 2 diabetes mellitus (T2DM) because both of these hormones have glucose-lowering actions. Tirzepatide, a synthetic peptide composed of 39 amino acids, functions as a dual receptor agonist of both the GIP and GLP-1 receptors. This unique mechanism of action has earned tirzepatide the nickname "twincretin." Tirzepatide's dual agonist activity may be the mechanism by which tirzepatide significantly reduces glycated hemoglobin levels and body weight in patients with T2DM as observed in phase 3 clinical trials. Besides its glucose-lowering and anti-obesity effects, tirzepatide has been reported to have potential cardiovascular benefits. In this review, we discuss the cardiovascular effects of tirzepatide based on the available preclinical and clinical data.

Key numbers

2.46%

Reduction in HbA1c

Reduction in HbA1c levels observed in patients treated with tirzepatide.

15.2 kg

Body weight loss

Weight loss achieved in the SURPASS-3 trial with tirzepatide at 15 mg.

4.8 mmHg

Systolic blood pressure reduction

Overall reduction in systolic blood pressure observed with tirzepatide treatment.

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The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist

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