What are the indications for Zepbound (tirzepatide)?

From the Guidelines

Zepbound (tirzepatide) is indicated for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity such as hypertension, type 2 diabetes, dyslipidemia, or obstructive sleep apnea. It should be used in conjunction with a reduced-calorie diet and increased physical activity. Zepbound is administered as a once-weekly subcutaneous injection, starting at 2.5 mg for the first 4 weeks, then increasing gradually to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and potentially up to 15 mg, with each dose maintained for at least 4 weeks before increasing. This gradual titration helps minimize gastrointestinal side effects. Zepbound works as a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist, which helps regulate appetite and food intake by affecting hunger centers in the brain while also slowing gastric emptying. Some key points to consider when prescribing Zepbound include:

• The importance of a comprehensive treatment plan that includes lifestyle modifications, such as diet and exercise, in addition to medication.
• The potential benefits of Zepbound in reducing weight and improving glycemic control, as seen in studies such as 1.
• The need to carefully select patients who are appropriate candidates for Zepbound, taking into account factors such as medical history, current medications, and potential contraindications. It's also important to note that Zepbound is not indicated for patients with type 1 diabetes, a history of pancreatitis, personal or family history of medullary thyroid carcinoma, or those with Multiple Endocrine Neoplasia syndrome type 2. As stated in 1, tirzepatide was FDA approved for treatment of obesity in November 2023, and a recent meta-analysis of RCTs reported that 15 mg weekly of tirzepatide was associated with greater weight loss compared with other medications. Additionally, studies such as 1 and 1 provide further guidance on the use of Zepbound in the context of type 2 diabetes management, highlighting its potential benefits in terms of weight loss and glycemic control. However, it is essential to consider the findings of more recent studies, such as 1 and 1, which provide a comprehensive review of the effectiveness and safety of newer pharmacologic treatments for type 2 diabetes, including Zepbound. Overall, Zepbound is a valuable treatment option for adults with obesity or overweight and at least one weight-related comorbidity, and its use should be guided by a thorough understanding of its benefits and potential risks, as well as the individual patient's needs and medical history.

From the FDA Drug Label

MOUNJARO® is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The indication for Zepbound (tirzepatide) is to improve glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise 2.

• Key points:
  • Type 2 diabetes mellitus: The primary indication for Zepbound.
  • Adjunct to diet and exercise: Zepbound should be used in conjunction with a healthy diet and regular exercise.
  • Improving glycemic control: The main goal of Zepbound treatment.

From the Research

Indications for Zepbound (Tirzepatide)

• Zepbound (tirzepatide) is indicated for the treatment of adults with type 2 diabetes as an adjunct to diet and exercise to improve glycemic control 3, 4, 5, 6, 7.
• It is also under investigation for use in chronic weight management, major adverse cardiovascular events, and the management of other conditions, including heart failure with preserved ejection fraction and obesity and non-cirrhotic non-alcoholic steatohepatitis 3.
• The SURPASS clinical trial program has demonstrated the efficacy and safety of tirzepatide in improving glycemic control and reducing body weight in adults with type 2 diabetes 3, 4, 5, 6, 7.
• Tirzepatide has also shown potential benefits in obesity management, with significant reductions in body weight and improvements in comorbidities and cardiovascular risk factors observed in the SURMOUNT program 7.

Clinical Trial Evidence

• The SURPASS trials have consistently shown that tirzepatide reduces HbA1c and body weight, with common adverse events related to gastrointestinal issues 3, 4, 5, 6, 7.
• Tirzepatide has been compared to other treatments, including semaglutide and basal insulin, and has demonstrated superior efficacy in reducing HbA1c and body weight 4, 6, 7.
• The SURMOUNT program has demonstrated the efficacy of tirzepatide in obesity management, with significant reductions in body weight and improvements in comorbidities and cardiovascular risk factors 7.

Mechanism of Action

• Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, which increases insulin secretion, reduces glucagon release, and promotes satiety and weight loss 3, 5, 6.
• The mechanism of action of tirzepatide is thought to be related to its ability to activate both GIP and GLP-1 receptors, which are key mediators of insulin secretion and glucose homeostasis 5, 6.