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Christopher McGowan, MD - How does Zepbound (tirzepatide) compare to Wegovy (semaglutide)?

Thumbnail of the video “Christopher McGowan, MD - How does Zepbound (tirzepatide) compare to Wegovy (semaglutide)?”
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Author: Christopher McGowan, MD
Categories: Health
Tags: health
Views: 1 · Last viewed: 2026-10-13 23:15 UTC

Short Summary

Main recommendation: Dr. Christopher McGowan presents Zepbound (tirzepatide) as the more effective of the two weight-loss medications, though he notes no head-to-head trial yet exists and that both drugs should be used under obesity medicine specialist guidance. Both are weekly injections that boost GLP-1 (and, for tirzepatide, GIP), with similar side effects and high costs. A direct comparison is pending the SURMOUNT-5 trial, a 700-patient trial expected to conclude in 2025.

Key Points

  • Mechanism: Wegovy (semaglutide) acts only on GLP-1, while Zepbound (tirzepatide) targets GLP-1 receptors and also boosts GIP (glucose-dependent insulinotropic polypeptide), with the two acting synergistically.
  • Efficacy from separate trials: In STEP-1 (Wegovy 2.4 mg), average weight loss at 68 weeks was 14.9% of body weight, with 32% losing at least 20%. In SURMOUNT-1 (Zepbound 15 mg), average loss at 72 weeks was 20.9%, with 50% losing at least 20%.
  • Side effects are similar: both commonly cause nausea, diarrhea, and constipation, mostly mild and temporary during dose escalation. Roughly 5 to 7% of patients in those trials stopped treatment due to side effects.
  • Serious rare risks shared by both include pancreatitis and gallbladder disease/gallstones, and both carry a boxed warning for medullary thyroid cancer, based on rodent studies.
  • Cost is a major barrier: insurance coverage is limited, and the average cost is about $1,000 or more per month (roughly $12,000 per year).

Details Worth Noting

  • Concrete instructions: Both medications are injected once weekly under the skin using single-use disposable pens. Dosing is escalated gradually over four to five months to a maximum of 2.4 mg for semaglutide and 15 mg for tirzepatide. The milligram strengths should not be directly compared across the two drugs.
  • Concrete instructions: Patients are advised to take these medications under the guidance of an obesity medicine specialist, who can determine the best option. Adding a registered dietitian or health coach for guidance and accountability is recommended to maximize effectiveness.
  • Concrete instructions: Stopping the medication once it is working is not recommended, since both are designed for long-term, continuous use.
  • Some patients anecdotally report fewer side effects with tirzepatide, but this has not yet been confirmed by clinical studies.
  • Wegovy was FDA approved for obesity in June 2021; Zepbound was recently approved by the FDA for obesity.
  • The speaker notes that trials have different patient populations, so cross-trial comparisons of efficacy are not strictly valid.

Bottom Line

Zepbound appears more potent on trial numbers, but the evidence is not yet a direct comparison, and cost and long-term use remain the practical deciding factors for most people.