Key takeaways

  • Tirzepatide activates receptors for two hormones, GIP and GLP-1.
  • In a trial comparing it directly with semaglutide, average weight loss was 20.2% versus 13.7% after 72 weeks.
  • Its side effects are similar to semaglutide, mostly involving the stomach and gut.

Tirzepatide is a once-weekly injection that acts on two hormone receptors. Like semaglutide, it activates the GLP-1 receptor. It also activates the receptor for GIP, another hormone the gut releases after meals that helps control insulin.

Researchers are still working out exactly how much the GIP part adds. What the trials show is that the combination produces larger average weight loss than GLP-1 drugs alone.

What is it approved for?

The FDA first approved tirzepatide for type 2 diabetes in 2022 and for chronic weight management in 2023. In late 2024 it was also approved to treat moderate to severe obstructive sleep apnea in adults with obesity.

What did SURMOUNT-1 show?

SURMOUNT-1 enrolled about 2,500 adults with obesity and no diabetes and followed them for 72 weeks. Average weight loss ranged from 15.0% to 20.9% across the treatment groups, compared with 3.1% on placebo.

How does it compare with semaglutide?

SURMOUNT-5 was the first trial to compare the two directly. Its 751 participants had obesity without diabetes. After 72 weeks, those on tirzepatide had lost 20.2% of their body weight on average, and those on semaglutide 13.7%.

Two details help put this in context. The trial was funded by tirzepatide’s manufacturer, and it was open-label, meaning participants knew which drug they were getting.

Side effects and risks

  • Nausea, diarrhea, vomiting and constipation, especially early on.
  • Warnings for gallbladder disease and pancreatitis.
  • The same boxed warning about thyroid C-cell tumors seen in rodent studies.
  • It can make birth control pills less reliable for a period after starting treatment.

The bottom line

Tirzepatide is well studied and, on average, more effective for weight loss than semaglutide in the one head-to-head trial so far. As with other drugs in this class, weight tends to come back after stopping, and long-term data are still being collected.

References

  1. Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-216.
  2. Aronne LJ, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025.
  3. U.S. Food and Drug Administration. Prescribing information for tirzepatide products.