Page data last changed: . Registry refreshes and identity assessments are separate from scientific content review.
Incretin backbone behind a generation of metabolic drugs.
Also known as: glucagon-like peptide-1
Part of the Metabolic & GLP-1 peptides cluster
Overview
Glucagon-like peptide-1 (GLP-1) is a 30–31-residue incretin hormone released by intestinal L-cells after a meal. It potentiates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and reduces appetite — but survives only 1–2 minutes in circulation, which is why every GLP-1 drug is a re-engineered version of this sequence.
Source & context
Biological / chemical source: Intestinal L-cells
Primary research or clinical context: Basis of diabetes & obesity therapeutics
What GLP-1 is
Glucagon-like peptide-1 is one of two incretin hormones (the other is GIP). It is cut from the proglucagon precursor in intestinal L-cells and secreted within minutes of eating. Its physiological job is to tell the pancreas that glucose is arriving from the gut, so insulin release is amplified in proportion to the meal — and only when glucose is elevated. That glucose-dependence is why GLP-1-based therapies rarely cause hypoglycaemia on their own, and it is the property every analog in this cluster inherits.
The amino acid sequence of GLP-1
The selected reference on this page is human GLP-1(7-36)amide: H-A-E-G-T-F-T-S-D-V-S-S-Y-L-E-G-Q-A-A-K-E-F-I-A-W-L-V-K-G-R, a 30-residue peptide with a C-terminal amide. This is the predominant circulating active form. GLP-1(7-37) is a distinct 31-residue free-acid form with an additional terminal glycine; its sequence and mass are not the selected reference here. The N-terminal histidine and the residues around it dock into the receptor's transmembrane core; the C-terminal half forms an α-helix that binds the receptor's extracellular domain.
Why the native hormone lasts only minutes
Dipeptidyl peptidase-4 (DPP-4) removes the first two residues (His-Ala) almost as soon as GLP-1 reaches the blood, producing GLP-1(9-36), which no longer activates the receptor. Neutral endopeptidase 24.11 cleaves the mid-chain, and the kidney clears what is left. The resulting plasma half-life is roughly one to two minutes. Every therapeutic analog is, at bottom, an answer to this one problem — see the half-life comparison guide for how each solves it.
Receptor and signalling
GLP-1 acts on the GLP-1 receptor, a class B GPCR expressed on pancreatic β-cells, gastric smooth muscle, vagal afferents, and neurons in the hypothalamus and hindbrain. Receptor activation raises cAMP through Gαs, which in β-cells amplifies glucose-stimulated insulin secretion and in the brain reduces hunger. The receptor is also present on α-cells (glucagon suppression) and in the heart and kidney, which is why cardiovascular and renal outcome trials of GLP-1 analogs have shown effects beyond weight and glucose.
| Tissue | Effect | Clinical relevance |
|---|---|---|
| Pancreatic β-cell | Glucose-dependent insulin secretion | HbA1c lowering with low hypoglycaemia risk |
| Pancreatic α-cell | Glucagon suppression | Lower post-meal glucose |
| Stomach | Slowed gastric emptying | Satiety; also the source of nausea early in treatment |
| Hypothalamus / hindbrain | Reduced appetite and food reward | Weight reduction |
| Heart, vessels, kidney | Anti-inflammatory and haemodynamic effects | MACE and kidney outcome trials |
From hormone to drug scaffold
Three engineering moves turn the two-minute hormone into a once-weekly medicine. First, protect position 8 from DPP-4 — by replacing alanine with α-aminoisobutyric acid (Aib) as in semaglutide, or by borrowing the DPP-4-resistant glycine of exendin-4. Second, add a fatty acid so the peptide rides on serum albumin instead of being filtered by the kidney: a C16 palmitate on liraglutide, a C18 or C20 fatty diacid on the once-weekly analogs. Third, adjust the sequence for solubility, helicity and — in the newer molecules — activity at a second or third receptor.
| Analog | DPP-4 protection | Albumin binding | Extra receptors | Half-life |
|---|---|---|---|---|
| Liraglutide | Steric shielding by side chain + self-association | C16 palmitate on Lys26 | — | ≈ 13 h |
| Semaglutide | Aib at position 8 | C18 diacid on Lys26 | — | ≈ 7 d |
| Tirzepatide | Aib at position 2 (GIP numbering) | C20 diacid on Lys20 | GIP receptor | ≈ 5 d |
| Retatrutide | Aib at position 2 | C20 diacid on Lys17 | GIP + glucagon receptors | ≈ 6 d |
The exendin-4 lineage
A second family of GLP-1 drugs descends not from human GLP-1 but from exendin-4, a 39-residue peptide from Gila monster saliva that happens to activate the human GLP-1 receptor and is naturally DPP-4-resistant (it has glycine at position 2). Exenatide is synthetic exendin-4; lixisenatide is a modified version. The exendin-4 C-terminal tail (…GGPSSGAPPPS-NH2) turned out to be so useful for receptor binding and stability that tirzepatide and retatrutide both borrow it, even though their N-terminal halves come from GIP.
Research context and what this page is not
This profile describes the biology of an endogenous hormone. Native GLP-1 itself is not a marketed medicine — its half-life makes it impractical — and “GLP-1 peptide” products sold online are usually analogs or unlabelled mixtures, not the hormone. The profiles linked from the class table below cover each analog's verified structure, half-life and trial data.
Sequence of the selected reference form
Sequence backbone for the reference form: Human GLP-1(7-36)amide. Termini, stereochemistry and modifications are described below.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Select the experimentally isolated human 30-residue amidated active form. GLP-1 is a family name: the selected structure does not represent GLP-1(7-37), precursor GLP-1(1-37), DPP-4 metabolites or radiolabelled tracers.
- Molecular form
- Human GLP-1(7-36)amide
- Species
- Homo sapiens
- Termini (N / C)
- Free alpha-amino group of L-histidine / L-arginine carboxamide (-CONH2)
Average reference mass · Molecular identity assessment: 2026-10-05
Reference policy updated: 2026-10-05
- PubChem PUG molecular properties and explicit molecular graph · 2026-10-05
- PubChem PUG stereochemistry and normalized structure identity · 2026-10-05
- Reviewed UniProt molecular sequence and processed-chain annotations · 2026-10-05
- Deacon et al. (1995), experimentally isolated human GLP-1(7-36)amide · 2026-10-05
His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH2
- Molecular formula
- C149H226N40O45
- Average reference mass
- ≈ 3,297.6
- Plasma half-life
- ≈ 1–2 min (DPP-4 cleavage + renal clearance)
- Receptors
- GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor signalling mainly through Gαs / cAMP
- Backbone
- Human GLP-1(7-36)amide
- C-terminus
- L-arginine carboxamide (-CONH2)
- Status
- Endogenous hormone — not a product
- PubChem CID: 16133831
Chemistry values: curated profile, PubChem.
Clinical development snapshot
ClinicalTrials.gov lists 2,145 registered studies with “GLP-1” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07249554 | Combination Therapy for Alcohol Use Disorder | Phase 2 | not yet recruiting | 2026-10-01 |
| NCT07775404 | A Study to Investigate the Efficacy and Safety of Elecoglipron in Asian Participants With Obesity or Overweigh | Phase 3 | recruiting | 2026-10-01 |
| NCT05254314 | Glucagon-Like Peptide-1 Receptor Agonist in the Treatment of Adult, Obesity-related, Symptomatic Asthma (GATA- | Phase 2 | active not recruiting | 2026-10-01 |
| NCT07224334 | Role of Alpha-to-beta Cell Communication to Adapt Insulin Secretion to Insulin Resistance. | Phase 1 | recruiting | 2026-10-01 |
| NCT07793929 | A Study to Evaluate the Impact of Renal Impairment on the Pharmacokinetics (PK) of Ribupatide | Phase 1 | recruiting | 2026-10-01 |
| NCT07734792 | Tirzepatide in Thrombectomy-Treated Acute Ischemic Stroke: A Randomized Trial | Phase 3 | not yet recruiting | 2026-10-01 |
The incretin & metabolic co-agonist class at a glance
| Peptide | Receptors | Length | Mass (Da) | Half-life | Status |
|---|---|---|---|---|---|
| GLP-1 (this page) | GLP-1R | 30 aa | ≈ 3,297.6 | ≈ 1–2 min (DPP-4 cleavage + renal clearance) | Endogenous hormone — not a product |
| Liraglutide | GLP-1R | 31 aa | ≈ 3,751.2 | ≈ 13 h (once-daily dosing) | Approved: Victoza (2010, T2D), Saxenda (2014, weight) |
| Semaglutide | GLP-1R | 31 aa | ≈ 4,113.6 | ≈ 7 days (≈ 145–165 h in clinical PK studies) | Approved: Ozempic (2017, T2D), Rybelsus (2019, oral T2D), Wegovy (2021, weight) |
| Tirzepatide | GIPR + GLP-1R | 39 aa | ≈ 4,813.5 | ≈ 5 days (≈ 117 h) | Approved: Mounjaro (2022, T2D), Zepbound (2023, weight; 2024, obstructive sleep apnoea) |
| Retatrutide | GIPR + GLP-1R + GCGR | 39 aa | ≈ 4,731 | ≈ 6 days | Investigational (phase 3) |
| Cagrilintide | Amylin / calcitonin | 37 aa | ≈ 4,409 | ≈ 7–8 days (159–195 h across doses in the phase 1b study) | Investigational (phase 3, as CagriSema with semaglutide) |
| Survodutide | GCGR + GLP-1R | 29 aa | ≈ 4,232 | Supports once-weekly dosing (published population estimates are on the order of several days) | Investigational (phase 3: SYNCHRONIZE obesity programme; MASH programme) |
| Mazdutide | GCGR + GLP-1R | 34 aa | ≈ 4,476 | Supports once-weekly dosing (published estimates are on the order of several days) | Approved in China (NMPA): chronic weight management (27 June 2025) and type 2 diabetes (2025) |
| Amycretin | GLP-1R + amylin | — | — | Supports once-weekly subcutaneous dosing | Investigational (phase 2 results published 2025; later-phase trials under way) |
Verified from PubChem, IUPHAR and the primary discovery papers cited on each profile. Half-lives are approximate population means from published pharmacokinetics.
GLP-1 — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Human GLP-1(7-36)amideAverage reference mass: 3,297.6 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- ChemistryPubChem formula updated to C149H226N40O45.
- Trials30 registered studies added on ClinicalTrials.gov (now 2145).
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about GLP-1
What is GLP-1?+
Glucagon-like peptide-1 (GLP-1) is a 30–31-residue incretin hormone released by intestinal L-cells after a meal. It potentiates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and reduces appetite — but survives only 1–2 minutes in circulation, which is why every GLP-1 drug is a re-engineered version of this sequence.
What Canadian product status is recorded for GLP-1?+
Canadian product status for GLP-1 has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the length of the selected reference form for GLP-1?+
The selected reference form (Human GLP-1(7-36)amide) has 30 residues or residue-derived units in its backbone. Other forms in this family may have a different length.
What is the amino acid sequence of GLP-1?+
The selected reference is human GLP-1(7-36)amide, HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR (30 residues, C-terminal amide). The distinct GLP-1(7-37) free-acid form adds a terminal glycine, giving HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG (31 residues).
What is the half-life of GLP-1?+
About one to two minutes. DPP-4 inactivates it by removing the N-terminal His-Ala dipeptide, and the kidney clears the fragments. Therapeutic analogs extend this to hours (liraglutide) or about a week (semaglutide, tirzepatide, retatrutide).
Is GLP-1 a peptide or a protein?+
A peptide. At 30–31 amino acids and roughly 3.3 kDa it is well under the size usually called a protein, and it has no folded tertiary structure beyond a C-terminal α-helix.
What does GLP-1 do in the body?+
It amplifies insulin release when glucose is high, suppresses glucagon, slows stomach emptying and reduces appetite via receptors in the brainstem and hypothalamus. Those four actions are the basis of every GLP-1 receptor agonist medicine.
Is GLP-1 the same as semaglutide or Ozempic?+
No. Semaglutide is an engineered analog that keeps 29 of GLP-1's 31 residues but adds an Aib substitution and a C18 fatty diacid side chain so it lasts about a week instead of two minutes. Ozempic and Wegovy are brand names for semaglutide products.
Further reading
- Metabolic peptidesGLP-1 Peptides Explained: GLP-1, Semaglutide, Tirzepatide, RetatrutideFrom endogenous GLP-1 to dual and triple agonists—an educational map of incretin peptide science and metabolic drug design.
- FoundationsGLP-1 vs GIP vs Glucagon: Incretin Receptor Classes ExplainedAn educational overview of the incretin and metabolic receptor classes—GLP-1, GIP, and glucagon—and how single, dual, and triple receptor agonism differ mechanistically.
- PharmacologyGLP-1 and Incretin Peptide Half-Lives Compared: From 2 Minutes to 8 DaysA sourced table of the plasma half-lives of native GLP-1, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, retatrutide, cagrilintide and the newer co-agonists — and the three engineering strategies (DPP-4 resistance, albumin binding, Fc fusion) that stretch minutes into a week.
Related peptides
References & further reading
- 1.Müller et al. (2019). Glucagon-like peptide 1 (GLP-1). Mol Metab
- 2.Klausen et al. (2022). The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br J Pharmacol
- 3.van Zuylen et al. (2024). Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration. Br J Anaesth
- 4.Kabahizi et al. (2022). Glucagon-like peptide-1 (GLP-1) signalling in the brain: From neural circuits and metabolism to therapeutics. Br J Pharmacol
- 5.McIntyre et al. (2024). The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS). Expert Opin Drug Saf
- 6.Lu et al. (2021). GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice and monkeys. Cell Rep Med
- 7.Silverii et al. (2025). Glucagon-like peptide 1 (GLP1) receptor agonists and risk for ischemic optic neuropathy: A meta-analysis of randomised controlled trials. Diabetes Obes Metab
- 8.Wasada (2004). [Glucagon-like peptide-1(GLP-1)]. Nihon Rinsho
- 9.PubChem — compound summary for Glucagon-like peptide 1 (CID 16133831)
- 10.Wikipedia — Glucagon-like peptide-1