Glucagon-like Peptide-1 (native)
/ Endogenous 30- or 31-residue intestinotrophic gut peptide (GLP-1(7-36)NH2 or GLP-1(7-37)); GLP-1R agonistALIAS · GLP-1 · GLP-1(7-36)NH2 · GLP-1(7-37) · Native glucagon-like peptide-1
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Tier 1 by virtue of the foundational status of the native peptide. The native peptide itself is not FDA-approved, but it is the pharmacological reference for the most successful peptide-drug class of the 2010s-2020s - exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide (a dual GLP-1/GIP agonist). Each analog has its own Open Assay page; this page describes the parent molecule.
Native GLP-1 is generated by tissue-specific post-translational processing of the proglucagon gene - the same gene that produces glucagon, GLP-2, and (via further processing) oxyntomodulin. In intestinal L cells, prohormone convertase 1/3 cleaves proglucagon to yield the 'major' bioactive forms GLP-1(7-37) (31 residues) and the C-terminally amidated GLP-1(7-36)NH2 (30 residues), both potent at the GLP-1 receptor.
GLP-1 signals through the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor coupled primarily to Gs and adenylyl cyclase. Receptor expression on pancreatic beta-cells drives glucose-dependent insulin secretion (the canonical incretin effect); central GLP-1R expression at the area postrema, nucleus tractus solitarius, and arcuate nucleus mediates satiety and reduced food intake; gastric GLP-1R activation slows gastric emptying.
The native peptide has a plasma half-life of ~2 minutes due to rapid N-terminal cleavage by dipeptidyl peptidase-4 (DPP-4). This short half-life motivated the analog drug-development strategies that produced exenatide (exendin-4 from Heloderma venom, DPP-4 resistant), liraglutide (acylated, albumin-bound), and semaglutide (further engineered for once-weekly dosing). DPP-4 inhibitors (sitagliptin and class) augment endogenous GLP-1 by preventing its enzymatic inactivation.
No FDA-approved native GLP-1 therapeutic - the native peptide's short half-life makes it impractical as a drug product. The clinical evidence base is the GLP-1-analog drug class: exenatide (FDA 2005), liraglutide (2010), albiglutide, dulaglutide (2014), lixisenatide, and semaglutide (subcutaneous 2017, oral 2019). Tirzepatide (dual GLP-1/GIP, FDA 2022) and the in-development triple agonists (retatrutide) extend the class. Each analog has its own evidence portfolio documented on its own Open Assay page.
Native GLP-1 in research infusions has a benign acute safety profile - mild nausea is the principal effect; the short half-life precludes chronic-administration questions. Class-level safety considerations from the GLP-1 analogs (gastrointestinal effects, pancreatitis-incidence questions, retinopathy in subgroup analyses, thyroid C-cell tumour rodent signal) apply to the analogs, not directly to the native peptide.
Regulatory status
- FDA status:
- Not FDA-approved
Vendor-sold 'GLP-1' research peptide is the native form, intended for laboratory use; it is not interchangeable with semaglutide or any of the approved analogs. The pharmacological activity will be similar in vitro but the in vivo half-life is roughly 1000-fold shorter than semaglutide.
The 'GLP-1' label encompasses two bioactive forms - GLP-1(7-36)NH2 and GLP-1(7-37) - which are pharmacologically near-equivalent but chemically distinct. Vendor product labelling does not always specify which form is supplied.