Peptide directorySkin, immune & repair

LEAP2

Found as an antibiotic, it turned out to be ghrelin’s natural opponent.

Where it comes from

Made in
Liver and the upper small intestine
Sent out by
Rises after eating and with obesity; falls with fasting and after bariatric surgery, the mirror image of ghrelin
Acts on
  • Ghrelin receptors in hypothalamus, pituitary and vagus
  • Bacteria, weakly

What it does

  • Blocks ghrelin from releasing growth hormone and driving hunger 2
  • Holds the ghrelin receptor quiet between meals
  • A weak antimicrobial at best, which is what it was first named for 1

In medicine

  • No medicine. The LEAP2-to-ghrelin ratio is a research marker in obesity and anorexia nervosa 3
  • Blood LEAP2 rises with body mass and falls with fasting in people, the mirror of ghrelin 3

Beyond the body’s own use

  • Obesity is the main interest: in mice, LEAP2 added to semaglutide produced more weight loss than semaglutide alone, and held it. Nothing has been given to a person 4
  • Because it is an inverse agonist rather than a simple blocker, it is also the tool used to ask what the ghrelin receptor does when nothing is bound to it, which is how it entered work on anorexia and on alcohol craving 2

Sources

  1. Krause et al., Isolation and biochemical characterization of LEAP-2, Protein Science 2003
  2. Ge et al., LEAP2 is an endogenous antagonist of the ghrelin receptor, Cell Metabolism 2018
  3. Mani et al., LEAP2 changes with body mass and food intake in humans and mice, Journal of Clinical Investigation 2019
  4. Holm et al., Sustained weight loss with combined LEAP2 and semaglutide treatment in mice, Diabetes 2025

This card describes what a medicine is for and what the evidence says; it recommends nothing. Talk to your clinician about anything you read here.