GLP-1 (glucagon-like peptide-1) is a 30-amino-acid hormone. L cells of the ileum and colon, and neurons in the brainstem, release it in response to food [1][2]. It is cut from the same precursor, proglucagon, as glucagon, but by different enzymes [4].

Receptor and effects

GLP-1 acts through the GLP-1R receptor (G protein Gs), found on β cells, in the stomach, brain, heart and kidney [1][2]. Its main effects:

  • it amplifies insulin secretion in a glucose-dependent way;
  • it suppresses glucagon secretion;
  • it slows gastric emptying;
  • it acts on satiety centres in the hypothalamus and brainstem [1][3].

Why native GLP-1 is so short-lived

The enzyme DPP-4 inactivates active GLP-1(7-36) amide within minutes, and the kidneys clear the fragments quickly. The native half-life is under two minutes [2][5]. Research analogues such as semaglutide and liraglutide are therefore built to resist DPP-4 and bind albumin, which stretches the duration to days.

GLP-1 next to the other axes

Mono-agonists act on GLP-1R only. Tirzepatide adds the GIPR receptor and in a head-to-head phase 3 trial gave a larger effect than semaglutide [6]. The next step, retatrutide, adds the glucagon receptor as well.

Reference material. Not medical advice. The molecules mentioned are for laboratory research only (RUO).

See also: GIP, glucagon, comparison of the three axes.