Can tirzepatide (Glucagon-like peptide-1 (GLP-1) receptor agonist) be stopped and semaglutide (GLP-1 receptor agonist) be given instead?

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Last updated: June 11, 2025View editorial policy

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From the Guidelines

Yes, tirzepatide can be stopped and replaced with semaglutide, as both are GLP-1 receptor agonists used to treat type 2 diabetes and obesity. When switching, it's generally recommended to discontinue tirzepatide and start semaglutide at its initial dose (typically 0.25 mg weekly for Ozempic or 3 mg daily for Rybelsus), then follow the standard dose titration schedule. No washout period is typically required between medications. Patients should expect similar but not identical effects, as tirzepatide works as both a GLP-1 and GIP receptor agonist (dual agonist), while semaglutide is solely a GLP-1 receptor agonist. This difference may result in variations in efficacy and side effects.

Key Considerations

  • Common side effects for both include nausea, vomiting, and diarrhea, which often improve with time 1.
  • Patients should monitor blood glucose levels closely during the transition and maintain communication with their healthcare provider to adjust dosing as needed.
  • The switch should be supervised by a healthcare provider who can tailor the approach to the individual's specific medical needs.

Efficacy Comparison

  • A recent meta-analysis of RCTs that included 12,371 adults with overweight or obesity without diabetes reported that 15 mg weekly of tirzepatide was associated with greater weight loss compared with 2.4 mg weekly of subcutaneous semaglutide (mean difference, 5.1%; 95% CI, 0.6%-9.8%) 1.

Safety and Monitoring

  • GLP-1 receptor agonists have been shown to decrease the risk of cardiovascular events in adults with overweight or obesity without diabetes 1.
  • Patients with a history of pancreatitis should use GLP-1 receptor agonists with caution 1.
  • An increased risk of diabetic retinopathy complications has been noted with semaglutide, predominantly in patients with a prior history of proliferative retinopathy 1.

From the Research

Switching from Tirzepatide to Semaglutide

  • Tirzepatide and semaglutide are both used in the treatment of type 2 diabetes, with tirzepatide being a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide being a selective GLP-1 receptor agonist 2.
  • Studies have shown that tirzepatide is noninferior and superior to semaglutide in terms of reducing HbA1c levels and body weight in patients with type 2 diabetes 2, 3.
  • However, there may be situations where switching from tirzepatide to semaglutide is necessary or beneficial, such as if a patient experiences adverse effects or if their treatment goals are not being met 4.

Considerations for Switching

  • When switching from tirzepatide to semaglutide, it is essential to consider the individual patient's needs and circumstances, including their medical history, treatment goals, and potential adverse effects 4.
  • The decision to switch should be made on a case-by-case basis, taking into account the patient's response to tirzepatide and their potential to benefit from semaglutide 4.
  • It is also important to note that semaglutide has been shown to have cardiovascular benefits, which may be an important consideration for patients with a high risk of cardiovascular events 5, 3.

Potential Benefits and Risks

  • Switching from tirzepatide to semaglutide may offer benefits such as improved tolerability, reduced adverse effects, or enhanced cardiovascular protection 5, 4.
  • However, there may also be risks associated with switching, such as changes in glucose control or weight, which should be carefully monitored and managed 4, 3.
  • The potential benefits and risks of switching from tirzepatide to semaglutide should be carefully weighed and discussed with the patient before making a decision 4.

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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