Semaglutide: Complete GLP-1 Agonist Research Profile
Ozempic research analogGLP-1 RA
Semaglutide is a 31-amino-acid GLP-1 receptor agonist that represents a significant advance in incretin-based research compounds. Its molecular design incorporates two key modifications from native GLP-1: an α-aminoisobutyric acid (Aib) substitution at position 8 that confers DPP-4 resistance, and a C-18 fatty diacid conjugated at lysine-26 that enables albumin binding for an extended pharmacokinetic profile. The resulting half-life of approximately 165 hours (7 days) makes it suitable for once-weekly dosing research protocols. Semaglutide has been the subject of the STEP clinical trial program, one of the largest weight management research programs ever conducted, with data published in the New England Journal of Medicine and The Lancet. It is also studied for cardiovascular risk reduction and potential applications in NASH, Alzheimer's disease, and other conditions beyond metabolic syndrome.
Technical Specifications
CAS Number
910463-68-2
Molecular Formula
C187H291N45O59
Molecular Weight
4113.58 g/mol
Amino Acids
31
Sequence
31-amino-acid GLP-1 analog with C-18 fatty diacid modification at Lys26
Purity
≥99% (HPLC)
Appearance
White lyophilized powder
Salt Form
Acetate
Solubility
Soluble in water at pH 7.4
Storage
-20°C lyophilized, 2-8°C reconstituted
Origin & Discovery
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk. It is a modified analog of human GLP-1(7-37) with two key substitutions (Aib8, Arg34) and a C-18 fatty diacid side chain conjugated at position 26 via a linker. This lipidation enables non-covalent albumin binding, extending the half-life to approximately 7 days.
Mechanism of Action
Semaglutide exerts its effects through agonism of the GLP-1 receptor, a class B G-protein coupled receptor expressed in multiple tissue types.
Pancreatic Beta Cells: GLP-1R activation on pancreatic beta cells enhances glucose-dependent insulin secretion through cAMP/PKA and Epac2 signaling pathways. This glucose-dependency means insulin secretion is amplified only when glucose is elevated, reducing hypoglycemia risk.
Hypothalamic Appetite Regulation: Semaglutide crosses the blood-brain barrier and activates GLP-1 receptors in the hypothalamic arcuate nucleus and other appetite-regulating centers, reducing food intake through modulation of POMC/CART (anorexigenic) and NPY/AgRP (orexigenic) neuron activity.
Gastric Emptying: GLP-1R activation delays gastric emptying via vagal afferent signaling, contributing to satiety and reduced postprandial glucose excursions.
Albumin Binding: The C-18 fatty diacid moiety enables reversible, non-covalent binding to serum albumin. This albumin association protects semaglutide from renal clearance and enzymatic degradation, accounting for the 7-day half-life that enables once-weekly administration.
Metabolic & Weight Management Research
The STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial program produced landmark data. Wilding et al. (2021) published in the New England Journal of Medicine that semaglutide 2.4 mg weekly produced a mean body weight reduction of 14.9% versus 2.4% with placebo over 68 weeks in adults with overweight or obesity (STEP 1, n=1961). Davies et al. (2021) published in The Lancet that semaglutide produced 17.4% weight reduction in adults with Type 2 diabetes over 68 weeks (STEP 2). These results represented the largest weight reductions achieved by any pharmacological agent in controlled trials at the time of publication.
Citations
Wilding JPH, et al. (2021) "STEP 1: Semaglutide 2.4mg in obesity." N Engl J Med, 384(11), 989-1002.
Davies M, et al. (2021) "STEP 2: Semaglutide in T2D and obesity." Lancet, 397(10278), 971-984.
Cardiovascular Research
Marso et al. (2016) published the SUSTAIN-6 trial in the New England Journal of Medicine, demonstrating that semaglutide reduced major adverse cardiovascular events (MACE) by 26% compared to placebo in patients with Type 2 diabetes at high cardiovascular risk (n=3297, median follow-up 2.1 years). The cardiovascular benefit appeared to be driven primarily by reduction in non-fatal stroke (39% reduction) and non-fatal myocardial infarction (26% reduction). This cardiovascular data expanded the research interest in semaglutide beyond metabolic endpoints into cardiovascular risk modification.
Citations
Marso SP, et al. (2016) "SUSTAIN-6: Semaglutide cardiovascular outcomes." N Engl J Med, 375(19), 1834-1844.
Frequently Asked Questions
What is Semaglutide?▼
Semaglutide is a 31-amino-acid GLP-1 receptor agonist with a C-18 fatty diacid modification that enables albumin binding and a ~7-day half-life. It is one of the most extensively studied metabolic research peptides, with STEP trial data published in NEJM and The Lancet.
How does Semaglutide compare to Retatrutide?▼
Semaglutide is a single-agonist (GLP-1R only) while Retatrutide is a triple-agonist (GLP-1/GIP/glucagon). Retatrutide's Phase 2 data showed 24.2% weight reduction at 48 weeks compared to semaglutide's 14.9% in STEP 1. Retatrutide adds glucagon receptor activation for thermogenesis.
What is the CAS number of Semaglutide?▼
The CAS registry number for Semaglutide is 910463-68-2.