What are Semaglutide and Tirzepatide?

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Both Semaglutide and Tirzepatide are injectable medications used initially for managing type 2 diabetes, that were found to have the remarkable and unexpected side effects of significant weight loss. They belong to a class of drugs known as GLP-1 receptor agonists. These medications mimic the action of a hormone called glucagon-like peptide-1 (GLP-1), which increases insulin secretion, decreases glucagon release, and slows gastric emptying. This combination helps lower blood sugar levels after meals and promotes fullness, which can contribute to reduced food intake. But the real mechanisms underlying their extraordinary effectiveness in weight loss lie in their effects within the brain. Both semaglutide and tirzepatide act on areas of the brain, including parts of the hypothalamus that regulate hunger, fullness, and cravings to turn off hunger signaling to a degree, which results in a state of negative energy balance that helps the majority of patients lose weight.

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Key Benefits of Semaglutide:

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• Effective Blood Sugar Control: Semaglutide has been shown to significantly lower HbA1c levels, a key marker of long-term blood sugar control.

• Weight Loss: Many patients experience substantial weight loss while taking Semaglutide, which is beneficial for those struggling with obesity.

• Cardiovascular Benefits: Studies have indicated that Semaglutide can reduce the risk of major cardiovascular events such as heart attack and stroke, in people who are at high risk for these, including those with type 2 diabetes.

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Key Benefits of Tirzepatide:

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• Enhanced Blood Sugar Control: Tirzepatide has shown superior efficacy in lowering HbA1c levels compared to other GLP-1 receptor agonists, including Semaglutide.

• Significant Weight Loss: Clinical trials have demonstrated that Tirzepatide can lead to more pronounced weight loss compared to Semaglutide, which is promising for patients with obesity.

• Dual Hormone Action: By targeting both GLP-1 and GIP receptors, the appetite and craving suppression is much stronger than with semaglutide alone, and the addition of the GIP component acts to decrease the nausea and vomiting side effect that can occur with semaglutide.

• Improvement in obstructive sleep apnea, a condition that has many negative effects on all aspects of health, has recently been validated and tirzepatide has received FDA-approval for treatment of this condition, as well as type-2 diabetes and obesity.

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Side Effects:

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• Both medications can cause gastrointestinal side effects, such as nausea, vomiting, and diarrhea. However, the incidence and severity of these side effects can vary between individuals.

• Tirzepatide’s dual-action mechanism may result in a different side effect profile compared to Semaglutide, and ongoing studies continue to evaluate these differences. Tirzepatide tends to cause fewer gastrointestinal side effects (nausea and vomiting) compared to semaglutide despite showing more significant weight loss over time.​​​

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Administration:

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• Both Semaglutide and Tirzepatide are administered via weekly subcutaneous injection. Semaglutide is available as an oral, FDA-approved medication called Rybelsus that is used to treat Type 2 diabetes. The oral form has not been studied for weight loss, but it does not result in weight loss comparable to the injectable forms.

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Who Should Consider These Medications?

For Diabetes Management:

• Patients with type 2 diabetes who struggle to control their blood sugar levels with oral medications may benefit from adding a GLP-1 receptor agonist like Semaglutide or Tirzepatide to their treatment regimen.

• Due to their positive impact on heart health, those at high risk of cardiovascular events may find additional benefits from these medications.

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For Weight Loss:

• The FDA-approved indications for use of Wegovy (semaglutide, Novo Nordisk) and Zepbound (tirzepatide, made by Eli Lilly) are individuals with obesity – with a BMI of 30 or higher, and individuals with a BMI of 27 who have at least 1 “comorbid” health condition are eligible for (but NOT assured of) insurance-coverage of these medications as part of a comprehensive weight loss plan. “Comorbid condition” means that patients have other health conditions that are either caused by or contributed to by the presence of obesity. High blood pressure, high cholesterol levels, and type-2 diabetes are all conditions that can often result from being overweight or obese. Semaglutide (Wegovy) is already FDA-approved specifically for weight loss in this these populations, as is Zepbound (tirzepatide). Tirzepatide’s superior weight loss efficacy makes it a promising option for patients seeking significant weight reduction or who have severe nausea and vomiting with semaglutide.

• We understand that many patients want to improve their health or quality of life through weight loss and that BMI is not a perfect indicator of healthy or optimal weight. We don’t believe that BMI alone should be the determining factor in whether a patient is granted access to these medications. We are also mindful of the potential harm to patients who have body dysmorphia, eating disorders, or low self-esteem. Our approach involves individual evaluations with one of our doctors or nurse practitioners to determine whether treatment with these medications is appropriate.

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