JAMA Original Investigation

Journal of the American Medical Association, January 2, 2024

Data from the SURMOUNT-4 Randomized Clinical Trial, a phase 3 open label withdrawal trial with 670 participants at 70 sites in 4 countries. Participants received once weekly subcutaneous injections of Tirzepatide for 36 weeks and then half were randomized to continue receiving drug or placebo for 52 weeks.

What’s Interesting about this article?

  • Tirzepatide is a single molecule that combines glucose -dependent insulintropic polypeptide (GIP) and GLP-1 receptor agonism resulting in synergistic effects on appetite, food intake and metabolism.
  • Tirzepatide was recently approved in the U.S. by the FDA, marketed as ZepboundTM.
  • Withdrawing Tirzepatide resulted in substantial regain of lost weight, whereas continued treatment maintained and augmented weight reduction.

JournalDoc Comments:

  • These findings are consistent with other studies that found that patients must remain on the new weight loss drugs or substantial weight gain occurs.
  • The requirement for long term use of Tirzepatide is worrisome because of loss of muscle and GI adverse effects reported with this class of drugs.
  • Until the need for maintenance therapy is solved, the new weight loss drugs should only be prescribed for patients with obesity and either/or diabetes or cardiovascular disorders.


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