Semaglutide Research, Specifications & Scientific Information

Introduction

Semaglutide is the compound that turned incretin pharmacology from a specialist interest into a mass one, and the chemistry behind it is unusually legible. It is a synthetic analogue of human glucagon-like peptide-1 altered in exactly three places: a non-standard residue at position 8 that blocks the enzyme which ordinarily clears native GLP-1 within minutes, an arginine substitution at position 34, and a fatty diacid hung from lysine 26 through a linker ^[1]. The third alteration is the consequential one. It binds the peptide reversibly to serum albumin, and in doing so converts a molecule with a half-life measured in minutes into one measured in days.

What sits on top of that chemistry is a clinical record deeper than almost anything else in this library: two cardiovascular outcome trials in two different populations, a kidney outcome trial stopped early at a prespecified interim analysis, and a liver trial with biopsy endpoints.

This page is a reference record. It sets out what has been published about semaglutide's structure, its receptor pharmacology, and the preclinical and clinical literature, with every source resolved against PubMed, Crossref or ClinicalTrials.gov at the time the page was built. It describes research. It does not describe use in people or animals, and it carries no guidance of any kind on handling the material.

What Is Semaglutide?

Semaglutide is a synthetic, acylated 31-residue peptide analogue of human glucagon-like peptide-1, developed by Novo Nordisk under the code NN9535 and first described in the peer-reviewed literature in 2015 ^[1].

Two things about its status need stating precisely, because they are routinely conflated.

It is an approved active ingredient. Semaglutide is the active ingredient of finished pharmaceutical products that hold U.S. Food and Drug Administration approval. That is a material difference from most compounds described in this library, which are investigational.

The approval belongs to those finished products, not to the chemical. Regulatory approval in the United States is granted to a specific finished product — a defined formulation, manufactured under a defined process, labelled for a defined indication — and not to a chemical in the abstract. Nothing about that approval extends to research-grade material supplied for laboratory use, whatever the molecule written on the label.

Structurally the compound belongs to the glucagon–secretin peptide superfamily. Functionally it is a single-receptor agonist: one molecule, one target, the GLP-1 receptor. That is the pharmacological fact that separates it from the dual and triple agonists developed after it.

Semaglutide Specifications

The 31-residue string above is the backbone recorded for semaglutide in the FDA/NCATS Global Substance Registration System under UNII 53AXN4NNHX, written in single-letter code. It is the backbone only, and single-letter code cannot express the molecule's non-standard chemistry. The discovery paper states the structure explicitly: semaglutide carries two amino acid substitutions relative to human GLP-1 — alpha-aminoisobutyric acid at position 8 and arginine at position 34 — and is derivatised at lysine 26. The residue at position 8 is not alanine, which is what the register's letter at that position would otherwise be read as; the substitution exists to block dipeptidyl peptidase-4 cleavage. The lysine 26 derivatisation is a C18 fatty diacid attached through a linker, and it is what confers the albumin affinity behind the reported half-life. The molecular formula and mass shown here correspond to the complete derivatised molecule and agree with PubChem CID 56843331 and with the supplier catalog record. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Semaglutide Work?

The GLP-1 receptor is a class B1 G protein-coupled receptor that signals through Gs to raise intracellular cyclic AMP. It is expressed on pancreatic islet cells, where its activation modulates glucose-dependent insulin secretion, and at a number of sites in the central nervous system, where it participates in the regulation of food intake.

Native GLP-1 activates the same receptor, and would be a poor pharmaceutical: dipeptidyl peptidase-4 cleaves it within minutes, and what survives is cleared renally almost as quickly. The whole design problem semaglutide solves is duration, not potency — and the solution reported in the discovery paper was to accept a lower receptor affinity in exchange for a much higher affinity for serum albumin ^[1].

Albumin is the reason this works. A peptide bound reversibly to a large plasma protein is protected from both proteolysis and glomerular filtration, and is released slowly enough to keep receptor occupancy roughly steady between weekly administrations. The molecule that results is pharmacologically unremarkable at its receptor and extraordinary in its residence time, which is the opposite of how most drug optimisation runs.

Semaglutide Mechanism of Action

In vitro research

The discovery characterisation reports the numbers behind that trade. Semaglutide's affinity for the GLP-1 receptor was measured at 0.38 ± 0.06 nM — approximately three-fold weaker than liraglutide, the once-daily analogue that preceded it — while its affinity for albumin was substantially higher ^[1].

The paper is explicit about which parts of the molecule do which job. The fatty acid moiety and the chemistry linking it to the peptide are identified as the two features that had to be optimised together to secure both albumin affinity and receptor potency; the amino acid substitutions at positions 8 and 34 are what secure stability against enzymatic degradation ^[1]. Those are separable design levers, and the published structure-activity work treats them as such.

Analytical characterisation of supplied material is a separate exercise from receptor pharmacology, and relies on liquid chromatography with mass spectrometric detection against a reference standard rather than on any biological assay.

What Is Semaglutide Being Researched For?

Registered clinical research on semaglutide has covered, in rough order of how early each programme reported:

• Type 2 diabetes mellitus — including a dedicated cardiovascular outcome trial for the subcutaneous product ^[2] and a separate one for the oral product ^[3].
• Obesity and overweight — a phase 3 programme in participants without diabetes ^[5] and a parallel trial in participants with type 2 diabetes ^[6].
• Cardiovascular outcomes in obesity without diabetes — an event-driven superiority trial in more than seventeen thousand participants ^[7].
• Chronic kidney disease in type 2 diabetes — a kidney outcome trial with a composite primary endpoint ^[8].
• Metabolic dysfunction-associated steatohepatitis — a phase 3 trial with liver histology as the primary endpoint ^[9].

Every one of those programmes studied pharmaceutical material, manufactured to a regulatory standard, administered under a registered protocol to a defined population under clinical supervision. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Semaglutide

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

SUSTAIN-6 — cardiovascular outcomes in type 2 diabetes

Population. 3,297 participants with type 2 diabetes on a standard-care regimen; at baseline 2,735 of them (83.0%) had established cardiovascular disease, chronic kidney disease, or both ^{[2, 10]}.

Endpoint and duration. Primary composite outcome: first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, over 104 weeks. The trial was powered as a noninferiority trial against a margin of 1.8 for the upper bound of the hazard ratio's confidence interval ^[2].

Result. The primary outcome occurred in 108 of 1,648 participants (6.6%) receiving semaglutide and 146 of 1,649 (8.9%) receiving placebo — hazard ratio 0.74, 95% CI 0.58 to 0.95, P < 0.001 for noninferiority. Nonfatal stroke occurred in 1.6% against 2.7%, hazard ratio 0.61, 95% CI 0.38 to 0.99. Rates of death from cardiovascular causes were similar between groups ^[2].

Adverse events. Fewer serious adverse events occurred in the semaglutide group, but more participants discontinued because of adverse events, mainly gastrointestinal. Rates of retinopathy complications — vitreous haemorrhage, blindness, or conditions requiring intravitreal treatment or photocoagulation — were significantly higher: hazard ratio 1.76, 95% CI 1.11 to 2.78, P = 0.02 ^[2].

Limitations. Designed to rule out excess cardiovascular risk rather than to demonstrate benefit; 104 weeks; the retinopathy signal was unexpected and remains the most-discussed finding of the trial.

STEP 1 — phase 3 in obesity and overweight

Population. 1,961 adults with a body-mass index of 30 or greater, or 27 or greater with at least one weight-related coexisting condition, none of whom had diabetes ^{[5, 12]}.

Endpoint and duration. Coprimary endpoints: percentage change in body weight, and a reduction of at least 5%. Randomised 2:1 to 68 weeks of subcutaneous semaglutide 2.4 mg once weekly or placebo, both with a lifestyle intervention ^[5].

Result. Mean change in body weight from baseline to week 68 was −14.9% with semaglutide against −2.4% with placebo, an estimated treatment difference of −12.4 percentage points, 95% CI −13.4 to −11.5, P < 0.001. Reductions of at least 5% occurred in 1,047 participants (86.4%) against 182 (31.5%); at least 10% in 69.1% against 12.0%; at least 15% in 50.5% against 4.9%. In absolute terms the change was −15.3 kg against −2.6 kg ^[5].

Adverse events. Nausea and diarrhoea were the most common, typically transient and mild to moderate, subsiding over time. Discontinuation owing to gastrointestinal events occurred in 4.5% against 0.8% ^[5].

Limitations. Sixty-eight weeks, in participants without diabetes, against a coprimary endpoint that is an anthropometric measure rather than a clinical outcome.

SELECT — cardiovascular outcomes in obesity without diabetes

Population. 17,604 participants aged 45 or older with preexisting cardiovascular disease and a body-mass index of 27 or greater, with no history of diabetes; 8,803 assigned semaglutide and 8,801 placebo ^{[7, 14]}.

Endpoint and duration. Primary endpoint a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, in a time-to-first-event analysis. Event-driven superiority design; mean exposure 34.2 ± 13.7 months, mean follow-up 39.8 ± 9.4 months ^[7].

Result. A primary endpoint event occurred in 569 of 8,803 participants (6.5%) receiving semaglutide 2.4 mg once weekly and 701 of 8,801 (8.0%) receiving placebo — hazard ratio 0.80, 95% CI 0.72 to 0.90, P < 0.001 ^[7].

Adverse events. Adverse events leading to permanent discontinuation of the trial product occurred in 1,461 participants (16.6%) against 718 (8.2%), P < 0.001 ^[7].

Limitations. A secondary-prevention population with established cardiovascular disease, which is not the population in which the compound is most often discussed; the trial does not separate how much of the effect is attributable to change in body mass and how much to anything else.

FLOW — kidney outcomes in type 2 diabetes with chronic kidney disease

Population. 3,533 participants with type 2 diabetes and chronic kidney disease defined by estimated glomerular filtration rate and urinary albumin-to-creatinine ratio thresholds; 1,767 assigned semaglutide 1.0 mg weekly and 1,766 placebo ^{[8, 15]}.

Endpoint and duration. Primary outcome a composite of major kidney disease events: onset of kidney failure, at least a 50% reduction in estimated glomerular filtration rate from baseline, or death from kidney-related or cardiovascular causes. Median follow-up 3.4 years, after early cessation was recommended at a prespecified interim analysis ^[8].

Result. The risk of a primary outcome event was 24% lower with semaglutide — 331 against 410 first events, hazard ratio 0.76, 95% CI 0.66 to 0.88, P = 0.0003. The mean annual estimated glomerular filtration rate slope was less steep by 1.16 mL per minute per 1.73 m², P < 0.001. Risk of major cardiovascular events was 18% lower (hazard ratio 0.82, 95% CI 0.68 to 0.98, P = 0.029) and risk of death from any cause 20% lower (hazard ratio 0.80, 95% CI 0.67 to 0.95, P = 0.01) ^[8].

Adverse events. Serious adverse events were reported in a lower percentage of the semaglutide group than the placebo group, 49.6% against 53.8% ^[8].

Limitations. Stopped early on a prespecified interim analysis, which tends to produce larger effect estimates than a trial run to completion; the eligibility thresholds define a specific band of kidney impairment and the result does not generalise outside it.

ESSENCE — phase 3 in metabolic dysfunction-associated steatohepatitis

Population. 1,197 participants with biopsy-defined metabolic dysfunction-associated steatohepatitis and fibrosis stage 2 or 3, randomised 2:1. The published analysis is a planned interim in the first 800 participants ^{[9, 16]}.

Endpoint and duration. Primary endpoints for part 1: resolution of steatohepatitis without worsening of liver fibrosis, and reduction in liver fibrosis without worsening of steatohepatitis, assessed at week 72 within a 240-week trial ^[9].

Result. Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of 534 participants receiving semaglutide 2.4 mg once weekly against 34.3% of 266 receiving placebo — estimated difference 28.7 percentage points, 95% CI 21.1 to 36.2, P < 0.001. Reduction in fibrosis without worsening of steatohepatitis was reported in 36.8% against 22.4%, difference 14.4 percentage points, 95% CI 7.5 to 21.3, P < 0.001. The combined endpoint was met by 32.7% against 16.1%. Mean change in body weight was −10.5% against −2.0%. Mean changes in bodily pain scores did not differ significantly between groups ^[9].

Adverse events. Gastrointestinal adverse events were more common in the semaglutide group ^[9].

Limitations. An interim analysis at 72 weeks of a trial designed to run to 240 weeks, in a histologically defined population with moderate or advanced fibrosis. Histological endpoints in liver disease are surrogate measures, and the clinical-outcome phase of the trial has not reported.

Preclinical Research on Semaglutide

Animal research

The rodent work published in 2020 answers a question the clinical trials cannot: where in the body the compound actually acts.

In rats, semaglutide did not cross the blood-brain barrier. It nevertheless reached the brainstem, the septal nucleus and the hypothalamus, interacting with the brain through the circumventricular organs and several sites adjacent to the ventricles — that is, through the places where the barrier is anatomically incomplete rather than through the barrier itself ^[4].

Mapping the consequences, the authors found central c-Fos activation in ten brain areas: hindbrain regions the compound reached directly, and secondary regions with no direct receptor interaction, among them the lateral parabrachial nucleus. Automated analysis of compound access, c-Fos activity, receptor distribution and brain connectivity pointed to neurons in the lateral parabrachial nucleus. Transcriptomic analysis of microdissected regions showed upregulation of prolactin-releasing hormone and tyrosine hydroxylase in the area postrema ^[4].

Behaviourally, the rodents showed modified food preference and reduced food intake, with body-mass reduction occurring without a decrease in whole-body metabolic rate ^[4].

The pharmacokinetic work sits alongside this. In mini-pigs, plasma half-life after intravenous administration was 46.1 hours, and mean residence time after subcutaneous administration was 63.6 hours — the figures that justified a once-weekly schedule in the human studies that followed ^[1].

Findings described in this section were observed in animals. Rodent and porcine models are standard preclinical tools, and nothing in them establishes anything about humans.

Other Areas of Semaglutide Research

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

The oral formulation. Semaglutide is unusual among peptides in having an orally administered product, achieved by co-formulation with an absorption enhancer. Its cardiovascular safety was assessed separately in PIONEER 6: 3,183 participants at high cardiovascular risk, median time in trial 15.9 months, with major adverse cardiovascular events in 61 of 1,591 (3.8%) against 76 of 1,592 (4.8%) — hazard ratio 0.79, 95% CI 0.57 to 1.11, P < 0.001 for noninferiority. Death from any cause occurred in 1.4% against 2.8%, hazard ratio 0.51, 95% CI 0.31 to 0.84. Gastrointestinal adverse events leading to discontinuation were more common with the oral product ^{[3, 11]}.

Overlapping populations. STEP 2 examined the same 2.4 mg weekly regimen in 1,210 adults who had both a body-mass index of at least 27 and type 2 diabetes, recruited from 149 outpatient clinics in twelve countries. Estimated change in body weight to week 68 was −9.6% against −3.4% with placebo, a treatment difference of −6.2 percentage points, 95% CI −7.3 to −5.2, P < 0.0001. Gastrointestinal adverse events, mostly mild to moderate, were reported in 63.5% of the 2.4 mg group against 34.3% on placebo ^{[6, 13]}. The comparison with the trial in participants without diabetes is instructive: the same regimen produced a smaller anthropometric change in the diabetic population.

Two constraints bound all of this. First, every result above belongs to a pharmaceutical product studied under a protocol. Second, the endpoints differ so much between these trials — a composite cardiovascular event, a percentage of body mass, a histological score — that they are not comparable to one another, and nothing here should be read as if they were.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Semaglutide vs Related Compounds

The distinction between semaglutide and the compounds it is usually set beside is receptor count, and nothing else stated here.

Receptor agonism

Semaglutide — GLP-1R only. Tirzepatide — GIPR and GLP-1R. Retatrutide — GIPR, GLP-1R and GCGR.

A different mechanism entirely

Cagrilintide is not an incretin analogue at all. It is a long-acting amylin analogue, acting through the calcitonin and amylin receptor families, and it has been studied both alone and co-administered with semaglutide.

Duration chemistry

Semaglutide, tirzepatide and retatrutide all use the same trick — a fatty acid on a lysine side chain, binding albumin — to reach a once-weekly schedule. Liraglutide, the compound semaglutide was designed to succeed, uses a shorter fatty acid and reaches only once-daily ^[1].

Regulatory position

Semaglutide and tirzepatide are active ingredients of approved pharmaceutical products in the United States. Retatrutide and cagrilintide are investigational. Approval is specific to a finished product and an indication and does not extend across a pharmacological class.

No comparison of effect between these compounds is made on this page. Where head-to-head trials exist they are registered, and their results belong to the papers that report them.

Chemical & Molecular Characteristics

Semaglutide is a modified 31-residue peptide. The backbone recorded in the FDA/NCATS Global Substance Registration System under UNII 53AXN4NNHX is HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG.

Three points qualify that string, and they are why this section sits separately from the specification table above.

The register's letters are not the whole molecule. The published structure is explicit: relative to human GLP-1, semaglutide carries alpha-aminoisobutyric acid at position 8 and arginine at position 34, and is derivatised at lysine 26 ^[1]. Alpha-aminoisobutyric acid has no single-letter code, so the letter standing at that position in the register's string should not be read as the residue actually present. The substitution is not decorative — it is what blocks dipeptidyl peptidase-4 cleavage.

The acylation is the mass. The fatty diacid and linker attached at lysine 26 account for a substantial part of the molecular mass, and they are the feature responsible for albumin binding and therefore for the compound's duration ^[1]. A bare 31-residue chain of the letters above would be a different molecule with entirely different pharmacokinetics.

The identifiers agree across registers. PubChem compound identifier 56843331 carries the molecular formula C187H291N45O59 and a mass of approximately 4,114 g/mol, which matches the value carried in the supplier catalog for the material offered as a laboratory reagent. CAS registry number 910463-68-2 is the number that validates against the CAS check-digit algorithm; variants differing in the final digit circulate in supplier listings and are transcription errors.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Lau J, Bloch P, Schäffer L, et al.. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide Journal of medicinal chemistry; 2015. PMID 26308095 doi:10.1021/acs.jmedchem.5b00726
2. Marso SP, Bain SC, Consoli A, et al.. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes The New England journal of medicine; 2016. PMID 27633186 doi:10.1056/NEJMoa1607141
3. Husain M, Birkenfeld AL, Donsmark M, et al.. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes The New England journal of medicine; 2019. PMID 31185157 doi:10.1056/NEJMoa1901118
4. Gabery S, Salinas CG, Paulsen SJ, et al.. Semaglutide lowers body weight in rodents via distributed neural pathways JCI insight; 2020. PMID 32213703 doi:10.1172/jci.insight.133429
5. Wilding JPH, Batterham RL, Calanna S, et al.. Once-Weekly Semaglutide in Adults with Overweight or Obesity The New England journal of medicine; 2021. PMID 33567185 doi:10.1056/NEJMoa2032183
6. Davies M, Færch L, Jeppesen OK, et al.. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial Lancet (London, England); 2021. PMID 33667417 doi:10.1016/S0140-6736(21)00213-0
7. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes The New England journal of medicine; 2023. PMID 37952131 doi:10.1056/NEJMoa2307563
8. Perkovic V, Tuttle KR, Rossing P, et al.. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes The New England journal of medicine; 2024. PMID 38785209 doi:10.1056/NEJMoa2403347
9. Sanyal AJ, Newsome PN, Kliers I, et al.. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis The New England journal of medicine; 2025. PMID 40305708 doi:10.1056/NEJMoa2413258
10. Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes 2013. NCT01720446
11. A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes 2017. NCT02692716
12. STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity 2018. NCT03548935
13. Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity 2018. NCT03552757
14. Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity 2018. NCT03574597
15. A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease 2019. NCT03819153
16. Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH) 2021. NCT04822181

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: Semaglutide specifications and lot documentation