What is the difference between Wegovy (semaglutide) and Zepbound (tirzepatide)?

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Last updated: May 22, 2025View editorial policy

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From the Guidelines

Wegovy and Zepbound are distinct medications for weight management, with Zepbound (tirzepatide) demonstrating greater weight loss in clinical trials due to its dual-action mechanism as a GLP-1 and GIP receptor agonist, compared to Wegovy (semaglutide) which is a GLP-1 receptor agonist alone. The key difference between these two medications lies in their mechanism of action and the hormones they target. Wegovy (semaglutide) works by mimicking the effects of the GLP-1 hormone, which is involved in appetite regulation and glucose-dependent insulin release 1. On the other hand, Zepbound (tirzepatide) has a dual-action mechanism, targeting both the GLP-1 and GIP receptors, which may explain its greater efficacy in weight loss, with average losses of 15-20% of body weight compared to Wegovy's 15% average 1.

Mechanism of Action and Efficacy

  • Zepbound (tirzepatide) has been shown to achieve greater weight loss compared to semaglutide in clinical trials, with a mean difference of 5.1% (95% CI, 0.6%-9.8%) 1.
  • The dual-action mechanism of Zepbound (tirzepatide) may contribute to its increased efficacy in weight loss, as it targets both the GLP-1 and GIP receptors, involved in blood sugar control and appetite regulation.
  • Both medications are self-administered once weekly via injection and are approved for adults with obesity or overweight with weight-related conditions.

Side Effects and Considerations

  • Both Wegovy (semaglutide) and Zepbound (tirzepatide) require gradual dose escalation to minimize side effects and commonly cause gastrointestinal side effects like nausea, vomiting, and diarrhea.
  • The choice between these medications often depends on insurance coverage, cost, individual response, and specific health considerations discussed with a healthcare provider.
  • It is essential to consider the potential benefits and risks of each medication, as well as individual patient factors, when making a decision about which medication to use for weight management 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Difference between Wegovy and Zepbound

  • Wegovy and Zepbound are both medications used for the treatment of type 2 diabetes and obesity, but they have different mechanisms of action and ingredients.
  • Wegovy is a brand name for semaglutide, a selective GLP-1 receptor agonist, whereas Zepbound is not mentioned in the provided studies, but based on the context, it seems to be related to tirzepatide, a dual GIP/GLP-1 receptor agonist 2, 3, 4, 5.
  • Tirzepatide has been shown to be more effective in reducing HbA1c and body weight compared to semaglutide in clinical trials 4, 5.
  • The most common adverse events associated with tirzepatide were gastrointestinal, including nausea, diarrhea, and vomiting, which were similar to those reported with semaglutide 4, 5.

Efficacy and Safety

  • Tirzepatide has been found to be noninferior and superior to semaglutide in terms of reducing HbA1c and body weight in patients with type 2 diabetes 4.
  • The incidence of hypoglycemia with tirzepatide was similar to that with placebo and lower than that with basal insulin 5.
  • Tirzepatide was associated with an increased incidence of gastrointestinal adverse events, including nausea, vomiting, and diarrhea, compared to placebo 5.

Comparison with Semaglutide

  • Tirzepatide has been shown to be more effective than semaglutide in reducing HbA1c and body weight in clinical trials 4, 5.
  • The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common 4, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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