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Zepbound™ (Tirzepatide), a Special Medicine For Diabetes And Obesity

Zepbound™ (tirzepatide) was approved by the U.S. Food and Drug Administration (FDA) on May 13, 2022. It is a dual receptor agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Research indicates that a once-weekly injection, combined with diet and exercise, can improve blood glucose levels in adults with type 2 diabetes mellitus (T2DM).

Zepbound™ (tirzepatide) injection activates the hormone receptors for GIP and GLP-1, making it a treatment for obesity. Zepbound is suitable for obese adults (BMI of 30 kg/m² or higher) or overweight individuals (BMI of 27 kg/m² or higher) with weight-related medical issues such as hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease, aiming to facilitate weight loss and weight maintenance.

Zepbound™ (Tirzepatide) Mechanism Of Action

The mechanism of action of Zepbound™ (tirzepatide) primarily involves the activation of the receptors for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Both receptors are B1-class G protein-coupled receptors found in pancreatic beta cells. Activation of these receptors leads to an increase in cyclic adenosine monophosphate (cAMP) and glucose-dependent insulin secretion, making them therapeutic targets for type 2 diabetes mellitus (T2DM) and obesity.

GLP-1 regulates insulin secretion, controls blood glucose, delays gastric emptying, and suppresses appetite. The mechanism of action of GIP is more complex; it can bidirectionally regulate insulin secretion, directly affect subcutaneous white adipose tissue, improve insulin sensitivity and fat buffering capacity, and enhance blood flow and storage capabilities.

Research indicates that tirzepatide not only enhances the activity of GLP-1 receptor agonists but also provides additional benefits from other activities. It more significantly improves insulin resistance and pancreatic beta-cell function. Its glucose-lowering effects are achieved through various aspects of improving beta-cell function, including enhanced insulin sensitivity, first/second-phase insulin secretion, and glucose sensitivity of beta cells.

Furthermore, tirzepatide also modulates beta-cell function through different signaling pathways, activating adenylate cyclase, increasing intracellular cAMP concentrations, thereby activating protein kinase A and cAMP-activated exchange protein directly (Epac). This complex mechanism of action means that tirzepatide is not simply adding the effects of GLP-1 and GIP receptor agonists but achieving efficacy beyond that of a single receptor agonist through the synergistic complementarity of both mechanisms.

The clinical efficacy of tirzepatide has been significantly demonstrated in the SURPASS series of clinical trials. These trials compared the effectiveness and safety of tirzepatide with commonly used antidiabetic drugs or placebos, and the conclusions showed that tirzepatide has significant glucose-lowering and weight-reducing effects.

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Clinical Efficacy Of Zepbound™ (Tirzepatide)

Clinical trial studies have demonstrated the clinical efficacy of Zepbound™ (tirzepatide):

SURPASS-1 Study: In patients receiving tirzepatide at doses of 5, 10, and 15 mg, glycated hemoglobin (HbA1c) decreased by 1.87%, 1.89%, and 2.07%, respectively. In contrast, the placebo group experienced only a 0.04% reduction in HbA1c.

SURPASS-2 Study: This study involved a head-to-head comparison between tirzepatide and semaglutide (1 mg). The results showed that the average reduction in HbA1c for patients in the 5, 10, and 15 mg tirzepatide groups was 2.09%, 2.37%, and 2.46%, respectively, while the semaglutide group had an average reduction of 1.86%. All doses of tirzepatide were superior to semaglutide, with the 15 mg tirzepatide group having 92% and 51% of patients achieving HbA1c levels of ≤ 6.5% and <5.7%, respectively.

SURPASS-3 Study: This study compared the efficacy and safety of tirzepatide with titrated insulin degludec, either alone or in combination with metformin or a sodium-glucose co-transporter 2 inhibitor (SGLT2i). The results indicated that the efficacy of tirzepatide at doses of 5, 10, and 15 mg was superior to titrated insulin degludec.

In summary, tirzepatide has demonstrated significant efficacy in reducing glycated hemoglobin (HbA1c), showing superiority over placebo and some commonly used antidiabetic drugs in clinical trials.

What Are The Side Effects Of Zepbound™ (Tirzepatide)?

Severe stomach issues have been reported in individuals using Zepbound™ (tirzepatide), sometimes reaching a serious level. If you experience severe or persistent stomach problems, it is crucial to inform your healthcare provider.

Kidney problems (renal failure) may arise due to fluid loss (dehydration) caused by diarrhea, nausea, and vomiting associated with Zepbound usage. Staying hydrated is important to reduce the risk of dehydration.

Gallbladder problems have been observed in some individuals using Zepbound. If you experience symptoms of gallbladder issues, including upper abdominal pain, fever, yellowing of the skin or eyes (jaundice), or clay-colored stools, it is important to inform your healthcare provider immediately.

Pancreatitis (inflammation of the pancreas) is a potential side effect. If you experience severe and persistent pain in the abdomen, with or without vomiting, discontinue the use of Zepbound and contact your healthcare provider immediately. Pain may radiate from the abdomen to the back.

Serious allergic reactions can occur. If you notice symptoms of a severe allergic reaction, such as swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing, severe rash or itching, fainting, or a rapid heartbeat, stop using Zepbound and seek medical help promptly.

Low blood sugar (hypoglycemia) risk may be higher if you use Zepbound with medications that can cause low blood sugar (such as sulfonylureas or insulin). Signs and symptoms of low blood sugar may include dizziness or lightheadedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shaking, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness, or feeling jittery.

Changes in vision have been noted in individuals with type 2 diabetes during Zepbound treatment. If you experience changes in vision while on Zepbound, inform your healthcare provider.

Depression or suicidal thoughts should be monitored. Pay attention to changes in your mood, behavior, feelings, or thoughts. If you notice any new, worsening, or concerning mental changes, contact your healthcare provider immediately.

Zepbound™ (Tirzepatide)

Things To Note Before Using Zepbound™ (Tirzepatide)

Before starting Zepbound™ (tirzepatide), it is important to discuss the following points with your healthcare provider:

Existing Health Conditions: Inform your healthcare provider about any other health conditions you may have, including pancreatic or kidney issues, or serious stomach problems such as gastroparesis (slow stomach emptying) or digestive issues.

Diabetes Medications: Report if you are taking any diabetes medications, such as insulin or sulfonylureas.

History of Diabetic Retinopathy: Provide information about your history of diabetic retinopathy.

Other Medications: Disclose any other prescription or over-the-counter medications, vitamins, or herbal supplements you are currently taking.

Pregnancy and Breastfeeding: If you are pregnant, planning to become pregnant, breastfeeding, or planning to breastfeed, discuss this with your healthcare provider. Zepbound may pose a risk to unborn babies, and it is unclear whether it passes into breast milk. Your healthcare provider can help determine the best approach for feeding your baby while using Zepbound.

Family History of Medullary Thyroid Cancer (MTC): If you or any family members have a history of a type of thyroid cancer called medullary thyroid cancer (MTC), do not use Zepbound.

Multiple Endocrine Neoplasia Type 2 (MEN 2): If you have type 2 multiple endocrine neoplasia syndrome (MEN 2), do not use Zepbound.

Severe Allergic Reactions: If you have had a severe allergic reaction to tirzepatide or any components of Zepbound, do not use it.

It’s crucial to provide your healthcare provider with a comprehensive medical history to ensure the safe and effective use of Zepbound and to identify any potential risks or contraindications based on your individual health profile.

How To Use Zepbound™ (Tirzepatide)

Read the instructions provided with Zepbound carefully and follow your healthcare provider’s guidance completely. Zepbound injections are administered subcutaneously (under the skin) in the abdomen (stomach), thigh, or upper arm.

Here are key points from the usage instructions:

Frequency: Use Zepbound once a week at any time of the day.

Rotation of Injection Sites: Change (rotate) the injection site weekly. Do not use the same site for each injection to avoid potential skin issues.

Injection Locations: Administer Zepbound subcutaneously in the abdomen, thigh, or upper arm.

Overdose: In the case of Zepbound overdose, contact your healthcare provider immediately and seek medical advice.

It’s important to strictly adhere to the prescribed dosage, frequency, and administration guidelines provided by your healthcare provider. If you have any questions or concerns about the usage of Zepbound, don’t hesitate to consult with your healthcare provider for clarification and guidance.

Zepbound™ (Tirzepatide) Price

Zepbound is expected to be released by the end of this year, with a total of six doses (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg), priced at $1,059.87 USD. This price represents a reduction of approximately 20% compared to the cost of a 2.4 mg injection of semaglutide. It’s important to note that the listed price does not reflect the typical out-of-pocket costs for patients covered by insurance and eligible for discounts.

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