Metabolic
A long-acting GLP-1 receptor agonist peptide analogue studied in incretin-receptor and preclinical metabolic research.
GLP-1 (SM) is a 31-residue acylated peptide analogue related to human glucagon-like peptide-1 (GLP-1). It is designed to bind the GLP-1 receptor, a class B G protein–coupled receptor, with extended duration through albumin-binding modifications. Research has examined its design and pharmacokinetics, receptor engagement at the structural and cellular level, and behavior in metabolic disease models spanning pancreatic, hepatic, and adipose tissue systems.
Last reviewed · For research use only.
Type
Synthetic peptide (acylated, 31 residues)
Molecular formula
C187H291N45O59
Molecular weight
~4,114 g/mol
CAS number
910463-68-2
Amino acids
31
Fatty acid chain
C18 diacid
Sequence
H-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys[C18-diacid/γ-Glu-AEEA₂]-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-NH₂
Modification
Aib8 and Arg34 substitutions; Lys26 C18 fatty-diacid acylation via gamma-Glu and two AEEA linkers.
A GLP-1 analogue incorporating Aib at position 8 and Arg at position 34, with Lys26 side-chain acylated to a C18 fatty diacid via a γ-Glu/AEEA spacer. It binds the extracellular domain and transmembrane pocket of GLP-1R, a class B G protein–coupled receptor. The Aib8 substitution confers resistance to DPP-4 cleavage; the C18-diacid side chain provides reversible albumin binding that extends serum half-life. Upon receptor engagement, intracellular signaling proceeds through the cAMP/PKA pathway and β-arrestin recruitment.
Research Focus
Used as a reference GLP-1R agonist in receptor-pharmacology and preclinical metabolic research.
Medicinal chemistry work on GLP-1 (SM) centered on extending the half-life of native GLP-1 through fatty-acid acylation for albumin binding. Lau et al. (2015) described the synthesis and characterization of acylated GLP-1 analogues incorporating α-aminoisobutyric acid (Aib) at position 8 and a C18 fatty diacid tethered via glutamate–AEEA spacers on Lys26, along with a Lys34→Arg substitution. These modifications were evaluated by ultracentrifugation binding assays with human serum albumin and by pharmacokinetic profiling in rodent and nonhuman primate models, characterizing serum protein binding and clearance. The design rationale and structural basis of long-acting GLP-1 analogues are surveyed in Knudsen and Lau (2019).
The structural basis of GLP-1 (SM)–receptor engagement has been characterized by cryo-EM. Zhang et al. (2021) resolved the complex of GLP-1 (SM) bound to the human GLP-1R in an active conformation with a heterotrimeric Gs protein (PDB 7KI0), mapping contact residues between the peptide’s N-terminal region and the extracellular and transmembrane domains of GLP-1R. The structural study examined hydrogen-bonding interactions with conserved receptor residues and the contribution of the modified positions (Aib8, C18-acyl side chain) to receptor conformation. Parallel cell-based assays in CHO and HEK expression systems have assessed GLP-1R activation endpoints — including cAMP accumulation and β-arrestin recruitment — following exposure to the peptide.
Pancreatic β-cell and isolated islet preparations are common model systems for examining incretin-receptor pharmacology. Studies have measured cAMP signaling and glucose-dependent insulin secretion in rodent and human β-cell cultures exposed to GLP-1 (SM), probing the relationship between receptor activation and secretion endpoints in both lean and metabolically stressed islet models. Off-target stability assays — including DPP-4 resistance profiling — have been reported alongside the β-cell pharmacology to characterize the peptide’s in vitro stability.
GLP-1 (SM) has been examined in hepatocyte and adipocyte model systems focused on metabolic signaling. Niu et al. (2022) conducted proteomics and metabolomics on liver tissue from high-fat-diet rodents, analyzing steatosis-associated proteins, lipid metabolism pathways, and inflammatory markers in the hepatic proteome. That dataset covers signaling through the AMPK/mTORC1 axis and gene expression profiles associated with lipid processing. Adipocyte studies have probed gene expression changes — including markers associated with lipid-metabolism pathways — in response to GLP-1R activation. The mechanistic landscape of GLP-1 receptor agonism in fatty liver animal models is surveyed in Polyzos et al. (2024).
GLP-1 (SM) has been applied in a range of rodent metabolic-syndrome research models. Diet-induced metabolic rodent models have been used to assess insulin-sensitivity and tissue-histology endpoints. Transgenic rodent lines (db/db, ob/ob genetic backgrounds) have served as systems for examining β-cell mass and proliferation markers. NAFLD/NASH-directed studies have focused on hepatic endpoints including lipid content, inflammatory gene expression, and proteomic profiles. Cardiovascular model work has examined vascular and myocardial signaling markers in rodent metabolic preparations. Pharmacokinetic profiling in these animal models has characterized the relationship between the albumin-binding modification and circulating duration.
Lyophilized
-20°C (-80°C long term)
powder typically stable ~24 months.
Reconstituted
-20°C ~1 month
2-8°C for short-term use only.
Avoid freeze-thaw; protect from light; keep sealed and dry. Self-associates in aqueous solution.
Reviews
Tsiampali C, Vachliotis ID, Goulas A, Polyzos SA (2024). Hormones (Athens) — Review of GLP-1 receptor agonist analogues in NAFLD/NASH animal models
Knudsen LB, Lau J (2019). Front Endocrinol — Review of long-acting GLP-1 analogue design and albumin-binding strategies
Aroda VR, Ahmann A, Cariou B, et al. (2019). Diabetes Metab — Comparative review across SUSTAIN 1–7 clinical studies; cited for study-design context
Reviews
Nauck MA, Quast DR (2021). Front Endocrinol — Review of findings from SUSTAIN 6 and PIONEER 6 clinical programmes; cited for study-design context
Shi FH, Li H, Cui M, et al. (2018). Front Pharmacol — Systematic review and meta-analysis of randomized clinical studies of once-weekly GLP-1 (SM); cited for study-design context
Meier JJ (2021). Front Endocrinol — Narrative review of subcutaneous and oral GLP-1 (SM) formulation efficacy data
Abusedera O, Sherif J, Smida M, Fredericks S (2025). J Clin Med — Systematic review and meta-analysis of GLP-1 (SM) effects on pancreatic β-cell function endpoints; cited for study-design context
Douros JD, et al. (2024). J Endocrinol — Review of GLP-1 receptor as a model for biased agonism in GPCR pharmacology
Rehman SU, Kolanu ND, Mushtaq MM, et al. (2024). Cureus — Systematic review of renal-endpoint studies examining GLP-1 (SM); cited for study-design context
Weiskirchen R, Lonardo A (2025). Med Sci (Basel) — Review of GLP-1 (SM) bench-to-bedside metabolic research; cited for study-design context
Clinical
Marso SP, et al. (2016). N Engl J Med — Randomized clinical study (SUSTAIN 6); cited for study-design context
Husain M, et al. (2019). N Engl J Med — Randomized clinical study (PIONEER 6); cited for study-design context
Lincoff AM, et al. (2023). N Engl J Med — Randomized clinical study (SELECT); cited for study-design context
Garvey WT, et al. (2022). Nat Med — Two-year randomized clinical study (STEP 5); cited for study-design context
Husain M, et al. (2020). Cardiovasc Diabetol — Post hoc analysis from SUSTAIN and PIONEER clinical studies; cited for study-design context
Husain M, et al. (2022). Cardiovasc Diabetol — Post hoc subgroup analysis from SUSTAIN 6 and PIONEER 6 clinical studies; cited for study-design context
Strain WD, et al. (2022). Stroke — Post hoc analysis from SUSTAIN 6 and PIONEER 6 clinical studies; cited for study-design context
Mellbin LG, et al. (2024). Eur Heart J — Post hoc analysis from SUSTAIN 6 and PIONEER 6 clinical studies; cited for study-design context
Alkhouri N, Herring R, Kabler H, et al. (2022). J Hepatol — Randomized phase II clinical study of GLP-1 (SM) combination; cited for study-design context
Primary research
Niu S, Chen S, et al. (2022). Front Endocrinol — Proteomics and metabolomics study examining GLP-1 (SM) in a rodent NAFLD model
Zhang X, Belousoff MJ, Liang YL, et al. (2021). Cell Rep — Cryo-EM structural study of GLP-1 (SM) bound to the human GLP-1R–Gs complex
Lau J, et al. (2015). J Med Chem — Design and pharmacokinetic characterization of long-acting acylated GLP-1 analogues
Cary BP, Deganutti G, Zhao P, et al. (2022). Nat Chem Biol — Cryo-EM analysis of conformational diversity among agonist-bound states of the GLP-1 receptor
Inia JA, Stokman G, Morrison MC, et al. (2023). Int J Mol Sci — GLP-1 (SM) effects on non-alcoholic steatohepatitis endpoints in Ldlr-/-.Leiden mouse model
Soto-Catalán M, Opazo-Ríos L, Quiceno H, et al. (2024). Int J Mol Sci — GLP-1 (SM) effects on hepatic steatosis and de novo lipogenesis markers in a rodent metabolic model
Zhu R, Chen S (2023). Front Endocrinol — Proteomic analysis of lipogenic protein expression in epididymal adipose tissue of GLP-1 (SM)-treated rodent metabolic model
Luo Y, Yang S, Zeng H, et al. (2025). Nutr Metab (Lond) — GLP-1 (SM) effects on pancreatic cell hyperplasia and gut microbiota in a high-fat-diet rodent metabolic model
Liu Y, et al. (2026). J Biomol Struct Dyn — Molecular dynamics study of GLP-1 (SM) binding interactions with human serum albumin
Research Use Only
These products are intended for research purposes only and are not for human consumption. Not FDA approved. Not intended to diagnose, treat, cure, or prevent any disease.
| Compound | Type | Molecular weight | CAS number |
|---|---|---|---|
| GLP-1 (SM)This page | Synthetic peptide (acylated, 31 residues) | ~4,114 g/mol | 910463-68-2 |
| GLP-3 (RT) | Synthetic peptide (acylated, 39 residues) | ~4,731 Da | 2381089-83-2 |
| GLP-1 (TRZ) | Synthetic linear peptide (dual GLP-1R/GIPR agonist; acylated, 39 residues) | ~4,814 g/mol | 2023788-19-2 |
| AOD-9604 | Synthetic peptide (cyclic, 16 residues) | ~1,815 g/mol | 221231-10-3 |
| MOTS-c | Mitochondrial-derived peptide (16 residues) | ~2,175 g/mol | 1627580-64-6 |
Comparison of laboratory reference specifications only. For research use only; not a therapeutic comparison.
