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Tirzepatide

FDA-approved

Also known as: Mounjaro, Zepbound

Structure source: RCSB PDB 7RBT: tirzepatide bound to the human GIP receptor (cryo-EM), peptide chain shown

Tirzepatide is a lab-made peptide of 39 amino acids, given by injection. It acts on the receptors for two gut hormones, GLP-1 and GIP, lowering appetite and blood sugar.

Approved for blood sugar control, with diet and exercise, in adults and children aged 10 and older with type 2 diabetes (as Mounjaro). Mounjaro is also approved to lower the risk of heart attack, stroke and cardiovascular death in high-risk adults with type 2 diabetes. As Zepbound, alongside diet and exercise, it is approved for long-term weight reduction in adults with obesity, or overweight with at least one weight-related condition. Zepbound is also approved for moderate-to-severe obstructive sleep apnea in adults with obesity.

How it works

  • It activates the GLP-1 receptor, which signals fullness to the brain and slows how fast the stomach empties.
  • It raises insulin release when blood sugar is high, and lowers glucagon, a hormone that raises blood sugar.
  • It also activates the GIP receptor, which improves insulin sensitivity and how fat tissue handles energy.
  • Activating both receptors together boosts insulin release more than activating GLP-1 alone.

Evidence

Weight loss in obesity

Strong human evidenceCEBM Level 1a

In a 72-week trial of 2,539 adults with obesity or overweight but no diabetes, the highest dose cut body weight by about 21% on average. In a later trial, people switched to placebo regained about 14% of their body weight in a year. Those who stayed on it kept losing.

Type 2 diabetes

Strong human evidenceCEBM Level 1a

It lowered HbA1c, a three-month average of blood sugar, by about 2 percentage points or more. In a head-to-head trial, it beat semaglutide on both blood sugar and weight.

Heart and blood vessels

Strong human evidenceCEBM Level 1a

In adults with type 2 diabetes and established heart or vessel disease, it was compared with dulaglutide, a drug with proven heart benefit. Rates of heart attack, stroke and cardiovascular death were similar; it was not shown to be better. In heart failure with preserved pumping function and obesity, it lowered the combined rate of cardiovascular death or worsening heart failure. The benefit came mainly from fewer worsening heart-failure events.

Caveats

  • Nausea, diarrhea, constipation and vomiting are common, mostly early on and after dose increases. They usually ease with time.
  • Pancreatitis (rare) and gallbladder disease (uncommon) are serious. Severe belly pain that will not go away needs prompt medical attention.
  • Rodent studies found thyroid C-cell tumors, so it is not used by people with a personal or family history of medullary thyroid cancer or MEN2.
  • It is also avoided in pregnancy and breastfeeding, after pancreatitis, with active gallbladder disease, and with severe stomach-emptying problems (gastroparesis).
  • Low blood sugar is uncommon on its own, but more likely when combined with insulin or a sulfonylurea.
  • Birth-control pills may work less well for four weeks after starting and after each dose increase. A non-oral or backup method covers this.
  • The weight lost includes some muscle as well as fat.

References

  1. Jastreboff AM, et al. N Engl J Med. 2022;387:205-216 (SURMOUNT-1).
  2. Aronne LJ, et al. JAMA. 2024;331:38-48 (SURMOUNT-4).
  3. Frías JP, et al. N Engl J Med. 2021;385:503-515 (SURPASS-2).
  4. Nicholls SJ, et al. N Engl J Med. 2025;393:2409-2420 (SURPASS-CVOT).
  5. Packer M, et al. N Engl J Med. 2025;392:427-437 (SUMMIT).

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Reviewed by Shubham Gupta, MD — Founder & President · October 31, 2026

This page is for education only. It is not medical advice. Decisions about any treatment belong with a physician who knows your history.