Single Regulator (SIA-31-C18): GLP-1 Receptor Agonist Research Profile
SIA-31-C18 is a 31-amino acid GLP-1 receptor agonist featuring a C18 fatty diacid side chain for extended half-life. The first member of the Regulator Series — structurally analogous in class to semaglutide. Full research profile, mechanism of action, and published literature review.
What is SIA-31-C18?
SIA-31-C18 — branded as the Single Regulator — is a synthetic 31-amino acid peptide designed as a selective GLP-1 receptor agonist. Its distinguishing structural feature is a C18 fatty diacid side chain conjugated via a linker to the peptide backbone, extending plasma half-life through albumin binding and enabling less-frequent dosing compared to first-generation GLP-1 peptides.
The "SIA" designation reflects its single-agonist pharmacology: exclusive targeting of the GLP-1 receptor without activity at GIP or glucagon receptors. This makes it mechanistically analogous in class to semaglutide, though SIA-31-C18 is a distinct research compound with its own amino acid sequence and structural characteristics.
The Regulator Series — comprising the Single (SIA-31-C18), Dual (DIA-39-C20), and Triple (TIA-39-C20) Regulators — represents a tiered approach to incretin receptor pharmacology, allowing researchers to study the incremental contribution of each receptor target across the weight-management peptide class.
Mechanism of action
GLP-1 receptor agonism. SIA-31-C18 binds and activates the glucagon-like peptide-1 (GLP-1) receptor, a class B G-protein-coupled receptor expressed in the pancreas, gut, brain, and peripheral tissues. GLP-1 receptor activation produces glucose-dependent insulin secretion from pancreatic beta cells, suppresses glucagon from alpha cells, slows gastric emptying, and reduces appetite centrally through hypothalamic GLP-1 receptor populations — particularly in the arcuate nucleus and nucleus tractus solitarius.
C18 fatty diacid side chain. The C18 fatty diacid modification enables reversible, non-covalent binding to circulating serum albumin. Albumin binding creates a depot effect that slows renal clearance and protects the peptide from dipeptidyl peptidase-4 (DPP-4) enzymatic degradation. This half-life extension mechanism is the same class of strategy used in the clinical development of long-acting GLP-1 analogues, enabling subcutaneous administration with extended dosing intervals.
Appetite suppression. Central GLP-1 receptor activation reduces food intake through multiple pathways: suppression of the orexigenic neuropeptide Y/AgRP neurons in the arcuate nucleus, activation of anorexigenic POMC/CART neurons, and engagement of the vagal-brain axis. The net effect is reduced meal size, prolonged satiety, and decreased preference for high-calorie foods in preclinical models.
Structural specifications
| Parameter | Value |
|---|---|
| Peptide length | 31 amino acids |
| Fatty acid chain | C18 fatty diacid (stearic diacid) |
| Receptor targets | GLP-1 receptor (selective) |
| Administration | Subcutaneous injection |
| Half-life extension | Via albumin binding (C18 side chain) |
| Series position | Single Regulator (first in the Regulator Series) |
Regulator Series comparison
SIA-31-C18 is the entry point in the Regulator Series, providing a GLP-1-only baseline against which the added pharmacological contributions of GIP (Dual Regulator) and glucagon (Triple Regulator) can be assessed in research settings.
| Compound | Receptor Targets | Chain Length | Fatty Acid |
|---|---|---|---|
| SIA-31-C18 (Single Regulator) | GLP-1 | 31 aa | C18 |
| DIA-39-C20 (Dual Regulator) | GLP-1 + GIP | 39 aa | C20 |
| TIA-39-C20 (Triple Regulator) | GLP-1 + GIP + Glucagon | 39 aa | C20 |
Research dosing
The following reflects dosing parameters used in research settings. For educational purposes only — not medical advice.
| Parameter | Research Range |
|---|---|
| Dose range | 0.25–2.4 mg per injection |
| Frequency | Once weekly (subcutaneous) |
| Titration | Start low (0.25 mg), escalate over 4-week intervals |
| Injection site | Abdomen, thigh, or upper arm (rotate sites) |
Reconstitution: Reconstitute with bacteriostatic water per vial specifications. Store reconstituted peptide refrigerated at 2–8°C. Use within 28 days of reconstitution. Do not freeze after reconstitution.
Research context
GLP-1 receptor agonism is the most extensively studied pharmacological mechanism in the weight management peptide class, with the clinical GLP-1 programme spanning three decades of research and multiple FDA-approved compounds. SIA-31-C18 provides a research-grade tool for investigating GLP-1 receptor biology, extended half-life fatty acid conjugation strategies, and single-receptor baseline pharmacology for comparison with dual and triple agonist compounds.
Researchers comparing the Regulator Series can use SIA-31-C18 as the GLP-1 monotherapy control against which the added metabolic contributions of GIP receptor co-agonism (DIA-39-C20) and glucagon receptor co-agonism (TIA-39-C20) can be quantified. For a broader discussion of incretin agonist class pharmacology, see our GLP-1 vs Dual Agonist vs Triple Agonist comparison.
Research sourcing: For research-grade GLP-1 class peptides with third-party COA documentation, Peptide Hub recommends Amino Club (partner code: PEPTIDEHUB). Affiliate link — we earn a commission at no cost to you.
Research references
- Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002. PubMed
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221–2232. PubMed
- Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109–121. PubMed
- Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER). N Engl J Med. 2016;375:311–322. PubMed
- Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2021;9:653–662. PubMed
- Drucker DJ. Mechanisms of action and therapeutic application of GLP-1. Cell Metabolism. 2018;27(4):740–756. PubMed