GLP-1 (1-37): unprocessed precursor of the gut hormone behind Ozempic
The full-length precursor of the gut hormone that semaglutide mimics; unlike the shorter active fragments, this form may also prompt intestinal cells to make insulin, used only as a lab research tool.
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.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
GLP-1 (1-37) is the full-length, unprocessed form of glucagon-like peptide-1 — the gut hormone that is the target of blockbuster diabetes and obesity drugs like semaglutide and liraglutide. The forms that circulate in the blood and act on the pancreas are short, 30- and 31-residue fragments (GLP-1 (7-36 amide) and GLP-1 (7-37)) that are produced when enzymes trim the first six residues off this precursor. The 37-residue (1-37) form was long considered biologically inert, but a 2003 paper showed it has its own distinct activity: it can push intestinal cells to start making insulin (Suzuki 2003). The peptide is part of the proglucagon-derived peptide (PGDP) family, which also includes glucagon, GLP-2, oxyntomodulin, and glicentin, all generated by tissue-specific processing of a single proglucagon precursor (Lafferty 2021).
History
GLP-1 emerged from the cloning and sequencing of the proglucagon gene in the early 1980s, when researchers found that the precursor protein encoded not only glucagon but two additional glucagon-like peptides. Subsequent work established that the bioactive incretin forms (7-36 amide and 7-37) are cleaved from (1-37) by prohormone convertases in intestinal L-cells, while pancreatic α-cells process proglucagon mainly into glucagon (Lafferty 2021). The pharmacology of the truncated active forms — their ability to amplify glucose-stimulated insulin secretion and suppress glucagon — drove the development of the GLP-1 receptor agonist drug class beginning with exenatide and continuing through liraglutide and semaglutide (Knudsen 2019). The (1-37) precursor itself remained an experimental curiosity until Suzuki and colleagues (2003) reported its insulin-inducing effect in intestinal epithelium.
What it does
In its native context, GLP-1 (1-37) is a precursor: tissue enzymes cleave it down to the shorter (7-36 amide) and (7-37) peptides that drive the incretin effect — glucose-dependent insulin release, glucagon suppression, slowed gastric emptying, and reduced appetite (Nauck 2004; Graaf 2016). The intact 37-residue peptide itself has a separate documented activity. Suzuki and colleagues (2003) showed that GLP-1 (1-37) induces insulin production in developing intestinal epithelial cells both in vitro and in vivo, with a weaker effect in adult tissue — suggesting the unprocessed form participates in a developmental programme that the cleaved active fragments do not.
Mechanism
GLP-1's bioactive fragments signal through the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor; the related proglucagon-derived peptide glucagon signals through the closely related glucagon receptor (GCGR). Both receptors share a characteristic two-domain architecture: a large extracellular domain that captures the C-terminal half of the peptide, and a seven-transmembrane bundle that the peptide's N-terminus engages to trigger Gαs coupling and cAMP signalling. The first full-length crystal structure of the glucagon receptor (Zhang 2017) and subsequent cryo-EM structures of GCGR bound to glucagon and to Gs or Gi heterotrimers (Qiao 2020) showed how peptide binding rearranges the transmembrane helices to open the intracellular G-protein binding site. Molecular dynamics work indicates that receptor activation does not follow a simple conformational-selection model — both the peptide and the G protein contribute to stabilising the active state (Mattedi 2020). Structural work on GLP-1R has similarly mapped the determinants of peptide binding to the seven-transmembrane core (Yang 2016). The extracellular domain of GCGR is itself a negative regulator of basal activity; antibodies that lock it in place act as inhibitors (Koth 2012). On the platform this card is linked to both GLP-1R and GCGR targets because the (1-37) precursor encompasses the full sequence of the GLP-1R-binding fragments while sharing extensive homology with glucagon and its receptor pharmacology.
Evidence
- Human: No human clinical trials of GLP-1 (1-37) itself. The clinical evidence base in this family is for the cleaved active forms and their long-acting analogs (liraglutide, semaglutide, dulaglutide, tirzepatide) (Knudsen 2019; Anastasiou 2025), not for the 37-residue precursor.
- Animal: GLP-1 (1-37) induces insulin production in developing rodent intestinal epithelium in vivo (Suzuki 2003).
- In vitro: GLP-1 (1-37) converts cultured intestinal epithelial cells into insulin-producing cells, with the effect strongest in developing tissue and weaker in adult cells (Suzuki 2003). Structural and biophysical studies of the related class B receptors GCGR and GLP-1R provide the mechanistic frame for how this peptide family engages its receptors (Yang 2016; Zhang 2017; Qiao 2020; Mattedi 2020; Koth 2012).
Known effects
- Insulin-producing cell induction in intestinal epithelium — preclinical, mouse and cell culture (Suzuki 2003)
- Precursor to incretin-active GLP-1 (7-36 amide) and (7-37) — biochemically established; the bioactivity of the cleaved forms is the basis of the entire GLP-1R agonist drug class (Lafferty 2021; Knudsen 2019)
Regulatory status
GLP-1 (1-37) is a research peptide with no approved therapeutic use. The truncated, modified analogs of the active (7-37) form — liraglutide, semaglutide, dulaglutide, tirzepatide — are FDA- and EMA-approved for type 2 diabetes and chronic weight management (Knudsen 2019; Anastasiou 2025), but those approvals do not extend to the (1-37) precursor itself.
Related peptides
GLP-1 (1-37) sits at the head of the proglucagon-derived peptide family. Related peptides include the cleaved active incretin forms GLP-1 (7-36 amide) and GLP-1 (7-37), glucagon, GLP-2, oxyntomodulin, glicentin, and glicentin-related pancreatic peptide — all generated by tissue-specific processing of the same proglucagon precursor (Lafferty 2021). The therapeutic landscape built on this family now extends to dual and triple receptor agonists combining GLP-1R, GCGR, and GIPR activity, such as tirzepatide (GLP-1R/GIPR) and retatrutide (GLP-1R/GCGR/GIPR) (Anastasiou 2025).
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Could the unprocessed form of GLP-1, which current drugs leave out, help the intestine grow its own insulin-producing cells?
If true, this could open a new way to treat Type 1 diabetes: helping the body rebuild its own insulin supply from cells already in the gut, instead of only managing blood sugar with injections.
Could the six extra amino acids at the start of the full-length GLP-1 precursor act as a switch that tells gut cells to become insulin-producing cells?
If this were true, it could reveal a natural way the gut controls its own hormone factories. This might help people with diabetes, because it could lead to ways to grow new insulin-producing cells inside the intestine instead of relying only on injections.
Could the full-length precursor, even though it is weaker than the trimmed form, still send signals to both sugar-raising and sugar-lowering pathways right after eating?
If true, it would mean the body naturally produces its own version of the newest dual-action diabetes drugs. Understanding this could help scientists design better meal-time therapies or figure out why some people process sugars better than others.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7428649663925171 | openfold3-mlx |
| ranking score | 0.8140402436256409 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.800 | global PDE — lower = better |
| disorder | 0.156 | fraction disordered |
| chain pair ipTM (A, B) | 0.743 | 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 | 471s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-23 |
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{pep10577,
sequence = {HDEFERHAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG},
target = {gcgr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}