Tirzepatide: A New Frontier in Diabetes Management

An estimated 530 million people worldwide are predicted to have diabetes, with a global prevalence of 10.5% among adults between the ages of 20 and 79. 

It is a chronic metabolic disease marked by high blood glucose levels.

Many patients find it difficult to attain ideal glycemic control without incurring side effects or complications, even with current medications.

But thanks to recent developments in pharmacotherapy, new medications like tirzepatide (marketed under the brand name Mounjaro) have been developed, providing potential new options for efficiently treating diabetes type 2.

In May 2022, Tirzepatide received FDA approval. Tirzepatide is also used off-label for the management of obesity.

Tirzepatide:

The first and only GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist FDA-approved for use in addition to diet and exercise to enhance glycemic control in individuals with type 2 diabetes is Mounjaro (tirzepatide).

Mounjaro is an injectable that can be administered once a week at any time of day, with or without meals, and comes in six doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.

It comes in an auto-injector pen with a hidden needle that is pre-attached and does not need to be handled.

It is noteworthy that tirzepatide has not been investigated in individuals with pancreatitis and is not licensed for the treatment of type-1 diabetes mellitus.

Additionally, it is not specifically approved for other types of diabetes, such as adult latent autoimmune diabetes.

Mechanism of Action

Tirzepatide targets the glucose-dependent insulinotropic polypeptide (GIP) receptor in addition to acting as an agonist of the glucagon-like peptide-1 (GLP-1) receptor once every week.

Tirzepatide improves insulin secretion, inhibits the release of glucagon, postpones stomach emptying, and encourages satiety by activating both GLP-1 and GIP receptors.

Improvements in glycemic management, weight loss, and possibly even advantages to the heart and kidneys are the results of this dual incretin action, which targets several pathophysiological pathways linked to diabetes.

Furthermore, adiponectin levels are likewise elevated by tirzepatide. Its dual agonism ability reduces hunger and results in a more marked decrease in hyperglycemia than GLP-1 agonist drugs alone.

Pharmacokinetics characteristics:¹

• Absorption: Approximately 80% of tirzepatide is bioavailable. Peak serum levels can be reached in as little as 8 to 72 hours. 

• Distribution: About 10.3 L is the mean apparent steady-state volume of distribution (Vd) for tirzepatide. Tirzepatide has a 99% binding strength to plasma albumin. 

• Metabolism: The peptide structure is broken down by proteolytic cleavage after injection. Additionally, amide hydrolysis and beta-oxidation are applied to the C20 fatty diacid composition.

• Excretion: Tirzepatide is excreted in urine and feces as metabolites. Its half-life of five days permits once-weekly use.

Clinical Efficacy 

Tirzepatide has demonstrated robust clinical efficacy in lowering body weight and HbA1c levels in a wide range of type 2 diabetes patients.

This includes individuals who had previously struggled to achieve appropriate glycemic control despite receiving prior therapy with other antidiabetic medications.

Tirzepatide has shown superior or comparable efficacy in lowering HbA1c and promoting weight loss compared to established GLP-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors.

One of the trials have indicated greater reductions in cardiovascular risk factors such as blood pressure and lipid levels.

Tirzepatide should only be taken if the possible benefits outweigh the possible risks to the developing foetus during pregnancy.

After explaining the potential teratogenic effects, patients of reproductive age should be prescribed tirzepatide. Before writing a tirzepatide prescription, doctors should also talk about starting a contraceptive method.

On tirzepatide medication, the effectiveness of oral hormonal contraception also decreases.

Safety Profile

Tiredness, vomiting, and diarrhea are the most often reported gastrointestinal side effects, albeit they are typically mild to moderate in intensity and transitory in character.

Overall, tirzepatide has a good safety profile. In order to reduce the risk of hypoglycemia, care should be taken while co-administering insulin or sulfonylureas.

Hypoglycemia rates are low, especially when administered as solo or in combination with metformin.

A study found that 10 and 15 mg of tirzepatide had better antidiabetic and weight-loss effects when compared to basal insulin (glargine or degludec); selective GLP1-RA (dulaglutide or semaglutide once weekly).

In particular, 15 mg of tirzepatide was dominant in reducing glycated hemoglobin, body weight, and fasting serum glucose. 

Regarding safety, there was no statistically significant difference between tirzepatide and GLP1-RA, and insulin produced less gastrointestinal problems.

Another study claims that, aside from hypoglycemia (tirzepatide 15 mg) and discontinuation (tirzepatide 10 mg, and 15 mg), tirzepatide's overall safety profile is comparable to that of GLP-1RAs.

Additionally, it demonstrated that increasing the dose could not increase the rates of hypoglycemia or severe gastrointestinal adverse events; tirzepatide 10 and 15 mg were linked to more frequent injection-site reactions, discontinuation, and nausea than 5 mg.

Also the rates of vomiting and diarrhea were dose-dependent within the 5–15 mg range.

Thyroid cancer in the medulla may occur, according to data from animal research. As of right present, it's unknown if humans would experience something similar.

Patients having a personal or family history of medullary thyroid cancer should not take tirzepatide due to the theoretical risk.

Therefore, worries about thyroid C-cell tumors, blindness, and possible pancreatitis call for continued observation and research.

Tirzepatide should also not be administered to patients with a history of MEN 2 (multiple endocrine neoplasia syndrome type-2).

Considerations for Patient Management

Tirzepatide therapy may have cardio-renal advantages, thus clinicians should evaluate patients' cardiovascular and renal conditions before starting the medication.

The choice and titration of therapies should be guided by the patient's unique treatment goals, preferences, and comorbidities.

Important aspects of diabetes care continue to be patient education about correct injection technique, therapy adherence, adverse effect recognition and management, and the significance of lifestyle adjustments.

Tirzepatide is a potentially beneficial addition to the antidiabetic drug arsenal, providing notable enhancements in weight control, glycemic control, and cardiovascular outcomes.

To clarify its long-term safety and efficacy profile, however, more research is necessary, especially in a variety of patient demographics and real-world environments.

Through thorough patient assessment, customized treatment plans, and vigilant monitoring, healthcare professionals are essential in optimizing tirzepatide therapy, which advances diabetes management toward better outcomes and enhanced patient quality of life.

1  Pharmacokinetics