GLP-1: the gut hormone that inspired Ozempic and Wegovy (natural form)
A natural hormone released in the gut after eating that tells the pancreas to release insulin; the molecule scientists used as a blueprint to create semaglutide and similar weight-loss drugs. Natural hormone, not a drug itself.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
Endogenous peptide — produced naturally and routinely synthesized for research
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Endogenous peptide — receptor binding and activity established in published literature
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What this is
GLP-1(7-37) is the 31-amino-acid active form of glucagon-like peptide-1, an intestinal hormone that tells the pancreas to release insulin in response to food. It is produced naturally in the gut after a meal, and it is the molecular scaffold from which GLP-1 receptor agonist drugs such as liraglutide and semaglutide were engineered.
The body generates two closely related active fragments from the same proglucagon precursor: GLP-1(7-37), whose sequence terminates as the free acid, and GLP-1(7-36)amide, which carries a C-terminal amide group instead. Both fragments promote insulin secretion in the isolated pancreas (Molecular Metabolism 2025). A C-terminally amidated reference form, GLP-1(7-37)-NH₂, has a molecular weight of approximately 3,355 Da (Prada Brichtova and colleagues, Soft Matter 2025). The raw sequence stored here (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG) represents the free-acid backbone; neither the amide cap nor any acylation is encoded in the single-letter string.
History
The biologically active truncated fragments — GLP-1(7-37) and GLP-1(7-36)amide — were identified after it became clear that the longer, initially characterised precursor form GLP-1(1-37) lacked insulinotropic activity. The N-terminally truncated forms were the species that recognised the pancreatic receptor and drove insulin release (British Journal of Pharmacology 2011). This discovery established GLP-1(7-37) as the reference active peptide and launched a medicinal-chemistry effort to create stabilised analogues with longer half-lives, ultimately producing the GLP-1 receptor agonist drug class.
What it does
GLP-1(7-37) binds the GLP-1 receptor (GLP-1R) on pancreatic beta cells and stimulates insulin release in a glucose-dependent manner — insulin secretion is amplified only when blood glucose is elevated, limiting hypoglycaemia risk. This glucose-dependent insulinotropic property is shared by both GLP-1(7-37) and GLP-1(7-36)amide and has been demonstrated in islet cells in vitro, in perfused pancreata, and in human subjects (ACS Pharmacology & Translational Science 2019; British Journal of Pharmacology 2011).
The N-terminal histidine at position 7 (His7) is essential for this activity. Removing even one residue from the N-terminus — producing GLP-1(8-37) — eliminates the insulinotropic response even though the rest of the sequence is intact. Perfused rat pancreas studies showed GLP-1(7-37) elicited a clear insulin response at 0.1–1 nM, while GLP-1(8-37) did not (British Journal of Pharmacology 2011).
Evidence
- Human: GLP-1(7-37) and GLP-1(7-36)amide exhibit glucose-dependent insulinotropic activity in human subjects (ACS Pharmacology & Translational Science 2019). As an endogenous hormone rather than a drug candidate, GLP-1(7-37) itself has not been developed into a clinical therapeutic; pharmacological development has focused on stabilised analogues.
- Animal: Insulin secretion stimulated in perfused rat pancreas at concentrations of 0.1–1 nM (British Journal of Pharmacology 2011).
- In vitro: Glucose-dependent insulinotropic activity characterised in isolated islet cells (ACS Pharmacology & Translational Science 2019).
Mechanism
GLP-1(7-37) is an agonist of the GLP-1 receptor, a class B G protein-coupled receptor. The free N-terminal His7 is a critical activation determinant: studies in perfused rat pancreas demonstrated that GLP-1(8-37), which lacks His7, has no insulinotropic effect despite sharing the remainder of the sequence (British Journal of Pharmacology 2011).
The peptide's backbone contains two lysine residues — Lys26 and Lys34 — that became key handles for medicinal-chemistry modifications. Attaching a fatty-acid chain to Lys26 via a γ-glutamic acid spacer markedly increases albumin affinity compared with the native peptide, extending circulating half-life and reducing renal clearance; this is the approach used in liraglutide design (Frontiers in Endocrinology 2019). Liraglutide is an acylated hGLP-1(7-37) analogue with the sequence HAEGTFTSDVSSYLEGQAAK(acyl)EFIAWLVRGRG and a C16 (palmitoyl) chain at Lys26 (Biochemical Pharmacology 2020).
Related peptides
- Semaglutide — a second-generation GLP-1(7-37)-derived analogue with a C18 fatty diacid chain at Lys26, enabling once-weekly dosing; shares the same 31-residue backbone with two amino-acid substitutions for protease resistance.
- GLP-1(7-36)amide — the C-terminally amidated sibling fragment, co-released from proglucagon and equally active at GLP-1R (molecular weight approximately 3,298 Da in amide form).
- Liraglutide — the first approved acylated hGLP-1(7-37) analogue; the γ-Glu-C16 chain at Lys26 enables once-daily pharmacokinetics.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8652577996253967 | openfold3-mlx |
| ranking score | 0.9196637272834778 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.706 | global PDE — lower = better |
| disorder | 0.154 | fraction disordered |
| chain pair ipTM (A, B) | 0.865 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 427s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-14 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep04450,
sequence = {HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG},
target = {glp-1r},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}