Tirzepatide is a dual GLP-1 and GIP analog that has got FDA approval for the treatment of patients with Type 2 Diabetes Mellitus.
It has been associated with marked weight loss of approximately 22% which is even greater than Wegovy, an FDA-approved weight loss drug, however, Tirzepatide’s FDA approval as a weight loss drug is pending.
Type 2 diabetes develops when a person poorly responds to the effects of insulin. This is called insulin resistance. Some people have a concomitant defect in insulin secretion as well.
It is characterized by various symptoms such as high blood pressure, increased triglycerides and fats, low insulin secretion, and frequent urination.
Various classes of medications are used to treat type 2 diabetes mellitus. These include:
- Insulin secretagogues like sulfonylureas and Meglitinides
- Biguanides (metformin)
- SGLT-2 inhibitors (Empagliflozin and Dapagliflozin)
- DPP-IV inhibitors (Sitagliptin and Vildagliptin)
- GLP-1 analogs (Semaglutide, Exenatide, Dulaglutide, and Liraglutide), and
- Dual GLP-1 and GIP analogs like Tirzepatide
These medications help diabetic patients either by increasing insulin production or reducing insulin resistance.
They also have an effect on body weight, blood pressure, lipids, hepatocytes, and beta-cells of the pancreas.
What is Tirzepatide?
Tirzepatide is the primary drug in the advanced class of medications for diabetes, called Dual GLP-1 and GIP analog.
It is sold by the name Mounjaro and is approved by the FDA for treating diabetes. It is also injected subcutaneously.
Like the GLP-1 analogs, Ozempic and others, it may cause constipation, severe abdominal pain, vomiting, loose motions, nausea, and abdominal discomfort.
There are certain hormones involved in the control of blood sugar such as GLP-1 and GIP. Tirzepatide is a drug that has a unique and advanced mechanism of action to activate both the receptors and improve levels of blood sugar.
Tirzepatide FDA Approval:
Tirzepatide got FDA approval very recently in May 2022 (REF) for the treatment of type 2 Diabetes Mellitus in patients who have inadequate control of diabetes with diet and exercise.
It can be used in combination with metformin, SGLT-2 inhibitors, Insulin, and sulfonylureas. However, its use in combination with DPP-IV inhibitors like Sitagliptin and Vildagliptin and GLP-1 analogs (Semaglutide, Dualglutide, and Liraglutide) is not recommended.
It should not be recommended to people with medullary thyroid cancer and multiple endocrine neoplasia syndrome type 2 in their family.
It is also not indicated in patients with pancreatitis or a history of pancreatitis.
How does it differ from GLP-1 analogs?
Tirzepatide activates both incretins, GLP-1 and GIP, unlike GLP-1 analogs which have no effect on GIP activation.
It has a higher affinity for GLP-1R than GLP-1 but it possesses lower activation for cAMP than GLP-1 does.
It is a bifunctional, unimolecular peptide prepared by Eli Lilly and Company. It enacts GLP-1R and GIPR and is made out of 39 amino acids, is converted into amide at the C-terminal, forms a Carbon 20 greasy diacid moiety employing a spacer associated with Lys20, and has a half-existence of 116.7 h.
It has a higher affinity for GLP-1R than GLP-1 does and its cAMP enactment action is fundamentally lesser (1-2 reduction in pEC50).
It has a lesser inclination towards GIPR than the other does (pIC50: 6.70 versus 7.87), and its cAMP action is around equivalent to that of GIP.6,8
Until this point in time, Tirzepatide significantly lowers HbA1c and weight of the body in type 2 diabetes mellitus patients.
Tirzepatide brought down Hemoglobin A1C by 22.8 mmol/mol and weight by ten kg in patients, which was the greatest achievement with any medication of all time.
Another investigation proved that a 15mg dose decreased Hemoglobin A1C by 2.1%.
Mechanism of action of Tirzepatide (Mounjaro):
Tirzepatide has a more noteworthy liking to GIP receptors than the other Glucagon-like Peptide 1 receptor, and this double agonist conduct has been displayed to create more prominent decreases of hyperglycemia contrasted with a particular Glucagon-like Peptide 1 receptor agonist.
However, at the Glucagon-like Peptide 1 receptor, it shows a tendency toward cAMP (a courier related with a guideline of lipid, glycogen, and sugar digestion) age, instead of β-arrestin enrollment.
This blend of inclination towards Gastric Inhibitory polypeptide receptor and fewer inclination properties towards Glucagon-like Peptide 1, propose this one-sided agonism increments insulin secretion.
It has likewise been proved to expand levels of adiponectin, an adipokine associated with the guideline of both lipid and glucose digestion, with a most extreme increment of 26% from gauge following twenty-six weeks, at the 10 mg dosage.
Tirzepatide use in Diabetes Mellitus Type 2:
Tirzepatide lowers blood glucose levels. It is a double GLP-1 and GIP receptor agonist. Glucagon-like peptide-1 (GLP-1) brings down blood sugar, including strengthening insulin emission and decreasing glucagon discharge during hyperglycemia.
Glucagon clearly goes against the activity of insulin; it raises the centralization of glucose in the blood by advancing glycogenolysis, which is the breakdown of glycogen (the structure wherein glucose is put away in the liver), and by animating gluconeogenesis. So Tirzepatide acts by lowering glucagon and hence blood glucose levels.
Tirzepatide weight loss effects:
A week after week infusion of the anti-diabetes drug Tirzepatide created a “significant and supported weight decrease” in fat grown-ups without diabetes, a review found.
The preliminary members lost up to a fifth of their body weight, by and large, contrasted and 3% in the placebo treatment bunch. Tirzepatide works by imitating two chemicals that assist with people feeling full in the wake of eating.
The efficacy of Tirzepatide has been found in all studies conducted on humans. In one such study involving 300 participants aged between 18 and 65 years, 48.6% reported decreased weight loss compared to baseline.
Another study involving 1550 volunteers, who were aged between 56 and 90 years showed only a 14.3% weight reduction at six months.
The average weight loss associated with Tirzepatide is ∼ 22% which is even greater than the latest blockbuster FDA-approved weight loss medicine, Semaglutide.
Tirzepatide use may cause the following side effects:
- Severe hypoglycemia when given in combination with Insulin or sulfonylureas
- Decreased appetite
- Abnromal sleeping patterns
- Abdominal pain
- Injection site reactions
- Hypersensitivity reactions
- Renal failure
Hazards of thyroid C-cell carcinoma:
In rodents, Tirzepatide caused thyroid C-cell growths. It is not well known whether Tirzepatide causes thyroid C-cell growths, including medullary thyroid carcinoma, in humans or not.
Its use should be avoided in ones having a family background of medullary thyroid carcinoma or patients with different endocrine neoplasia disorder type 2.
Educate one’s expected risk for MTC and potential side effects of thyroid growths (eg, constant dryness, dysphagia, mass in the neck, difficulty in breathing). Routine utilization of thyroid ultrasound or monitoring of serum calcitonin is not recommended.
Tirzepatide and Pregnancy
Information is deficient in regards to using it in pregnant females. Based on studies, there might be dangers to the baby from Tirzepatide during pregnancy.
Use during pregnancy is not recommended.
Ineffectively controlled diabetes in pregnancy increments maternal risk for diabetic ketoacidosis, toxemia, unconstrained early terminations, preterm conveyance, and conveyance confusions
Ineffectively controlled diabetes enhances the fetal risk for significant birth deformities, stillbirth, and macrosomia-related horribleness.
Tirzepatide and Contraception:
Tirzepatide might diminish the successful results of oral hormonal contraceptives inferable from delayed emptying of the stomach.
This emptying is greatest after the main portion and lessens after some time.
Tell patients utilizing oral hormonal contraceptives, to change to a non-oral preventative strategy or to add an obstruction technique for contraception for a very long time after inception and for a long time after each portion heightens.
It is prescribed to adults in the following amounts:
- 5 mg/0.5mL weekly as a subcutaneous injection
- 10 mg/0.5mL subQ weekly
- 15 mg/0.5mL weekly as a subQ injection
Cost of Tirzepatide:
Tirzepatide can only be purchased on a doctor’s prescription. Its retail price is around $12,666 per year