In recent years, Tirzepatide has emerged as one of the most promising new medications in the treatment of Type 2 Diabetes Mellitus (T2DM) and obesity. It is Developed by Eli Lilly and marketed under the brand name Mounjaro. Now-a-days it is a game changer in the treatment of type 2 Diabetes Mellitus and Obesity.

What is Tirzepatide?

Tirzepatide is a dual Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) receptor agonist (RA). Tirzepatide mimics the actions of both GLP-1 and GIP, which are incretin hormones released after eating. These hormones help to lower blood sugar levels. A Phase 2b study established a wide dose range of Tirzepatide, which showed clinically meaningful and superior Hemoglobin A1c (HbA1c) control with greater weight loss and an acceptable tolerability profile compared with a selective GLP-1 RA (Receptor Agonist), dulaglutide. In addition, Tirzepatide treatment resulted in marked reduction of serum triglyceride concentration, a cardiovascular (CV) risk factor in type 2 diabetes mellitus (T2DM). Preclinical and early clinical studies have provided evidence that Tirzepatide has characteristics similar to other potent GLP-1 RAs

What is the Mechanism of action of Tirzepatide?

Tirzepatide augments the body’s natural insulin response to food while simultaneously reducing appetite and slows the gastric emptying. Its mechanisms include:

oGlucose-dependent insulin secretion stimulation (Promoting insulin release when blood sugar levels are high)

oGlucago secretion suppression (a hormone that rises blood sugar)

oWeight reduction (by delaying stomach emptying time and causing satiety)

oBlood pressure reduction

These attributes are considered to play a role in the cardiovascular (CV) protective efficacy of Tirzepatide. The magnitude of glycaemic control and weight reduction appears to be more pronounced with Tirzepatide than with most GLP-1 RAs. Moreover, the reduction in serum triglyceride is greater when compared with GLP-1 selective RAs. These clinically relevant additional benefits are probably the result of the simultaneous activation of both GIP and GLP-1 pathways by Tirzepatide.

When the additional benefits are prolonged during a longer treatment period, they could contribute to CV protection in patients with T2DM as observed by GLP-1 RAs, hence significantly reduces the incidence of Major Adverse Cardiovascular Events (MACE) composite outcomes, which comprised nonfatal myocardial infarction (MI), nonfatal stroke, and death from CV causes, in patients with T2DM and with increased risk for CV events.

Dosage and Administration:

Clinical Trial Data:

Clinical trial the SURMOUNT-1 have demonstrated remarkable outcomes with

average weight loss of 20.9% at 15 mg dose after 72 weeks

It showed robust glycemic control and weight reduction

Key Benefits:

•Superior HbA1c control compared to other GLP-1 RAs

•Significant weight loss

•Acceptable tolerability profile

•Reduction in serum triglycerides (CV risk factor)

Outcome:

•Improve T2DM outcomes

•Reduce obesity-related comorbidities

•Mitigate cardiovascular risks

Indications approved by FDA:

•Type 2 Diabetes Mellitus: Approved in 2022 under the name inj. Mounjaro developed by Eli Lilly

•Obesity/Weight Loss: In the November 2023, a higher-dose version (branded as Zepbound) was approved for obesity in adults or overweight conditions with at least one co-morbidity.

Side Effects and Considerations:

Like other GLP-1 RAs, Tirzepatide can also cause:

•Nausea

•Vomiting

•Diarrhoea or constipation

•Decreased appetite

These effects are usually mild and patients tend to develop tolerance to these adverse effects over time. However, the drug is contraindicated for people with a history of medullary thyroid cancer or certain types of endocrine tumours.

Future Prospects:

Tirzepatide is currently under trial for other indications, like:

•Heart failure with preserved ejection fraction (HFpEF)

•Non-alcoholic steatohepatitis (NASH)

•Prevention of type 2 diabetes in high-risk individuals

Conclusion:

Tirzepatide advocates a significant advancement in the treatment of metabolic syndrome. Its dual-action helps to provide superior blood sugar control and weight loss compared to existing therapies.