Tirzepatide

Tirzepatide Is a dual glucose-dependent insulinotropic polypeptide-GLP-1 receptor agonist.

Tirzepatide, sold under the brand name Mounjaro, is a medication used for the treatment of type 2 diabetes.

Approved for chronic weight management (Zepbound).

Tirzepatide is given by subcutaneous injection.

It is a glucose dependent insulin tropic polypeptide (GIP) and glucagon like peptide-1 receptor agonist (GLP-1).

Side effects may include:  nausea, vomiting, diarrhea, constipation, upper abdominal discomfort, and abdominal pain.

Routes of administration- Subcutaneous.

Drug class – Antidiabetic, GLP-1 receptor agonist

Bioavailability 80%.

Protein binding-Albumin

Metabolism is by  proteolytic cleavage, β-oxidation of fatty diacid section and amide hydrolysis.

Elimination half-life-Five days

Excretion Urine and feces

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are hormones involved in blood sugar control.

Tirzepatide activates both the GLP-1 and GIP receptors, which leads to improved blood sugar control.

Tirzepatide is indicated to improve blood sugar control in adults with type 2 diabetes, as an addition to diet and exercise.

It should not be used in people with a personal or family history of medullary thyroid cancer or in people with multiple endocrine neoplasia syndrome type 2.

Adverse effects: similar adverse effects to other established GLP-1 receptor agonists.

These effects occur largely within the gastrointestinal tract:  nausea, diarrhea and vomiting, which increased with the increased dosage amount.

Other side effects are dyspepsia, constipation, abdominal pain, dizziness and hypoglycaemia.

It is an analogue of gastric inhibitory polypeptide (GIP), a hormone that stimulates the release of insulin from the pancreas. 

It is a linear polypeptide of 39 amino acids that has been chemically modified by lipidation to improve its uptake into cells and its stability to metabolism.

It has a greater affinity to GIP receptors than to GLP-1 receptors, and this dual agonist behavior has been shown to produce greater reductions of hyperglycemia compared to a selective GLP-1 receptor agonist.

At the GLP-1 receptor, tirzepatide shows bias towards cAMP, a messenger associated with regulation of glycogen, sugar and lipid metabolism generation.

GLP-1 agonism increases insulin secretion.

It has also been shown to increase levels of adiponectin, an adipokine involved in the regulation of both glucose and lipid metabolism.

Tirzepatide is an analog of the human GIP hormone used to optimize the uptake and metabolism of the compound, that allows for a much longer half life, extending the time between doses, because of its high affinity to albumin.

In trials comparing tirzepatide to semaglutide, an injected analogue of the hormone GLP-1), it showed minor improvement of reductions (2.01%–2.30% depending on dosage) in glycated hemoglobin tests relative to semaglutide (1.86%).

It has also been shown to be effective in reducing insulin resistance, with a reduction of around 8% from baseline, with fasting levels of IGF binding proteins like IGFBP1 and IGFBP2 increasing  following tirzepatide treatment, increasing insulin sensitivity.

A meta-analysis showed that over one-year of clinical use, tirzepatide was observed to be superior to dulaglutide, semaglutide, degludec, and insulin glargine with regards to glycemic efficacy and obesity reduction.

In a phase 3 double-blind, randomized, controlled trial of non-diabetic adults with a body mass index of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, were randomized to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg): The mean percentage change in weight at week 72 was −15.0% with 5-mg weekly doses of tirzepatide, −19.5% with 10-mg doses, and −20.9% with 15-mg doses and −3.1% with placebo.