Liraglutide Research, Specifications & Scientific Information

Introduction

Liraglutide is the compound that proved a peptide hormone could be turned into a once-daily medicine, and it did so by a piece of chemistry that now looks obvious and did not at the time. Native glucagon-like peptide-1 is cleared from plasma within minutes. The Novo Nordisk series that produced liraglutide asked a narrow question — what happens if a fatty acid is hung off the peptide so that it binds reversibly to serum albumin — and answered it systematically across chain lengths and attachment positions, reporting the structure-activity relationship rather than a single winner ^[1]. Liraglutide is the member of that series that went forward.

It is also, for this library, the compound with the longest and least ambiguous clinical record in its family. A cardiovascular outcome trial in 9,340 participants, a phase 3 programme in adults with and without type 2 diabetes, a trial in children, and a phase 2 trial with liver biopsies as the endpoint all report in the peer-reviewed literature and all resolve against their registries.

This page is a reference record. It sets out what has been published about liraglutide'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 Liraglutide?

Liraglutide is a synthetic, acylated 31-residue peptide analogue of human glucagon-like peptide-1, developed by Novo Nordisk under the code NN2211 and derived from the acylation series first reported in 2000 ^[1].

Its regulatory position needs two sentences, not one, because they are routinely collapsed into each other.

It is an approved active ingredient. Liraglutide is the active ingredient of finished pharmaceutical products that hold U.S. Food and Drug Administration approval. Those products are marketed under separate brand names, at different labelled amounts, for different indications — which is itself the clearest demonstration that an approval is a statement about a product rather than about a molecule.

The approval belongs to those finished products. 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.

Liraglutide Specifications

The 31-residue string above is the backbone recorded for liraglutide in the FDA/NCATS Global Substance Registration System under UNII 839I73S42A, written in single-letter code. Unlike most peptides in this family, liraglutide carries no non-standard residue in its backbone: relative to human GLP-1(7-37) the only substitution is arginine for lysine at position 34, and that substitution is expressible in single-letter code. What the string does not express is the acylation. A palmitic acid — a straight sixteen-carbon fatty acid — is attached to the side chain of lysine 26 through a glutamic acid spacer, and that group is the whole reason the molecule persists in plasma long enough to be administered once daily rather than continuously. Two public registers carry slightly different formulae for the complete molecule: PubChem CID 16134956 records C172H265N43O51 at approximately 3751 g/mol, while the Global Substance Registration System records C172H267N43O52 at 3751.202 g/mol, a difference of one water molecule that reflects how each register treats the C-terminal group. Both are reproduced here rather than reconciled, because reconciling them would mean choosing one register's convention and presenting it as settled. 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 Liraglutide 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.

The design problem liraglutide solves is residence time. Native GLP-1 is an excellent agonist and a hopeless pharmaceutical: dipeptidyl peptidase-4 cleaves it within minutes, and the fragments are cleared renally almost as fast. A peptide bound reversibly to albumin is protected from both, and is released slowly enough to keep receptor occupancy roughly steady between administrations.

What is distinctive about liraglutide, read against the compounds that succeeded it, is how little else was changed. Its backbone carries a single conservative substitution and no non-standard residue at all. The whole of its pharmacokinetic behaviour is carried by one sixteen-carbon fatty acid and the glutamic acid spacer that attaches it. Later analogues in the same family added backbone protection against dipeptidyl peptidase-4 and lengthened the acyl group, and moved from a daily schedule to a weekly one; liraglutide is what the minimal version of the idea achieves.

Liraglutide Mechanism of Action

In vitro research

The structure-activity series behind the compound is unusually legible because it was published as a series rather than as a single molecule. Native GLP-1 was measured at a half-maximal effective concentration of 55 pM at the cloned human GLP-1 receptor. Many of the fatty-acid derivatives matched or exceeded that potency despite carrying substantial substituents, which was not the expected result ^[1].

Three findings from that work set the design constraints for everything in this family that followed. Every derivative carrying a fatty acid of twelve carbons or longer was markedly protracted relative to native GLP-1. Derivatisation with linear fatty acids up to sixteen carbons was tolerated almost anywhere in the C-terminal part of the peptide without much loss of potency — but the longer the fatty acid, the more potency was lost, so chain length is a trade rather than a free parameter. And attaching two fatty acid substituents, or modifying the N-terminus for metabolic stability at the same time as acylating, cost considerable potency ^[1].

That last point explains a structural difference between liraglutide and its successors that is otherwise easy to misread as an oversight. Liraglutide has no position-8 modification because, in this chemistry, the two modifications interfered with each other; the later analogues solved that interference with a linker rather than by abandoning one of them.

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 Liraglutide Being Researched For?

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

• Type 2 diabetes mellitus in adults — the LEAD programme, including a head-to-head glycaemic trial against exenatide ^[2].
• Obesity and overweight — a phase 3 trial in adults without diabetes ^[4] and a parallel trial in adults with type 2 diabetes ^[5].
• Cardiovascular outcomes in type 2 diabetes — an event-driven trial in participants at high cardiovascular risk ^[7].
• Non-alcoholic steatohepatitis — an investigator-led phase 2 trial with paired liver biopsies ^[6].
• Type 2 diabetes in children and adolescents — a randomised trial in participants aged ten to under seventeen ^[8].

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 Liraglutide

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.

LEADER — cardiovascular outcomes in type 2 diabetes

Population. 9,340 participants with type 2 diabetes and high cardiovascular risk, randomised to liraglutide or placebo added to standard care ^{[7, 10]}.

Endpoint and duration. Primary composite outcome in a time-to-event analysis: first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was noninferiority against a margin of 1.30 for the upper boundary of the hazard ratio's 95% confidence interval. Median follow-up 3.8 years ^[7].

Result. The primary outcome occurred in 608 of 4,668 participants (13.0%) receiving liraglutide against 694 of 4,672 (14.9%) receiving placebo — hazard ratio 0.87, 95% CI 0.78 to 0.97, P < 0.001 for noninferiority and P = 0.01 for superiority. Death from cardiovascular causes occurred in 219 (4.7%) against 278 (6.0%), hazard ratio 0.78, 95% CI 0.66 to 0.93, P = 0.007. Death from any cause occurred in 381 (8.2%) against 447 (9.6%), hazard ratio 0.85, 95% CI 0.74 to 0.97, P = 0.02. Rates of nonfatal myocardial infarction, nonfatal stroke and hospitalisation for heart failure were nonsignificantly lower ^[7].

Adverse events. The most common adverse events leading to discontinuation were gastrointestinal. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group ^[7].

Limitations. The trial was designed as a noninferiority trial; superiority was met but the prespecified exploratory outcomes carried no adjustment for multiplicity, and the authors say so. The population is one at high cardiovascular risk and the result does not generalise outside it.

SCALE Obesity and Prediabetes — phase 3 in adults without diabetes

Population. 3,731 adults without type 2 diabetes, with a body-mass index of at least 30, or at least 27 with treated or untreated dyslipidaemia or hypertension. Mean age 45.1 years, mean body mass 106.2 kg, 78.5% women, 61.2% with prediabetes ^{[4, 12]}.

Endpoint and duration. Coprimary endpoints: change in body mass, and the proportions of participants reaching reductions of at least 5% and more than 10% of initial body mass. Fifty-six weeks, randomised 2:1, double-blind, with lifestyle counselling in both arms ^[4].

Result. At week 56, mean change in body mass was −8.4 ± 7.3 kg with liraglutide against −2.8 ± 6.5 kg with placebo, a difference of −5.6 kg, 95% CI −6.0 to −5.1, P < 0.001. Reductions of at least 5% occurred in 63.2% against 27.1%, and of more than 10% in 33.1% against 10.6%, both P < 0.001 ^[4].

Adverse events. The most frequently reported were mild or moderate nausea and diarrhoea. Serious events occurred in 6.2% of the liraglutide group against 5.0% of the placebo group ^[4].

Limitations. Fifty-six weeks, with coprimary endpoints that are anthropometric measures rather than clinical outcomes, and with last-observation-carried-forward imputation in the primary analysis.

SCALE Diabetes — phase 3 in adults with type 2 diabetes

Population. 846 adults with type 2 diabetes and a body-mass index of 27.0 or greater, glycated haemoglobin 7.0% to 10.0%, on none to three oral agents, at 126 sites in nine countries ^{[5, 13]}.

Endpoint and duration. Three coprimary endpoints at week 56: relative change in body mass, and the proportions reaching reductions of at least 5% and of more than 10%. Fifty-six weeks randomised 2:1:1, with a twelve-week off-drug observational follow-up ^[5].

Result. Change in body mass was 6.0% (6.4 kg) in the 3.0 mg group, 4.7% (5.0 kg) in the 1.8 mg group and 2.0% (2.2 kg) with placebo. The estimated difference against placebo was −4.00 percentage points, 95% CI −5.10 to −2.90, for 3.0 mg, and −2.71 percentage points, 95% CI −4.00 to −1.42, for 1.8 mg, both P < .001. Reductions of 5% or more occurred in 54.3% and 40.4% against 21.4%; reductions of more than 10% in 25.2% and 15.9% against 6.7% ^[5].

Adverse events. More gastrointestinal disorders were reported in the 3.0 mg group than in the 1.8 mg or placebo groups. No pancreatitis was reported ^[5].

Limitations. Fifty-six weeks, anthropometric coprimary endpoints, and — as the authors state directly — no evidence on longer-term efficacy or safety.

Ellipse — type 2 diabetes in children and adolescents

Population. 135 participants aged ten to under seventeen with type 2 diabetes, body-mass index above the 85th percentile, glycated haemoglobin 7.0–11.0% on diet and exercise alone or 6.5–11.0% on metformin. Mean age 14.6 years; 134 received at least one administration ^{[8, 14]}.

Endpoint and duration. Primary endpoint the change from baseline in glycated haemoglobin at 26 weeks, within a 26-week double-blind period followed by a 26-week open-label extension. All participants received metformin throughout ^[8].

Result. At 26 weeks, mean glycated haemoglobin had fallen by 0.64 percentage points with liraglutide and risen by 0.42 percentage points with placebo — an estimated treatment difference of −1.06 percentage points, P < 0.001 — widening to −1.30 percentage points by 52 weeks. Fasting plasma glucose fell at both time points with liraglutide and rose with placebo ^[8].

Adverse events. The number of participants reporting any adverse event was similar between groups (84.8% against 80.9%), but overall rates of adverse events and of gastrointestinal adverse events were higher with liraglutide ^[8].

Limitations. 135 participants. The comparison is against metformin alone, not against another GLP-1 receptor agonist, and the extension period was open-label.

Preclinical Research on Liraglutide

Animal research

The rodent work published in 2014 addresses a question the clinical trials cannot answer: which cells the compound acts on, and whether it acts in the brain directly.

The answer is more specific than the question. In rats, the body-mass reduction produced by liraglutide did not depend on GLP-1 receptors in the vagus nerve, the area postrema or the paraventricular nucleus, and the compound did not activate the GLP-1-producing neurons of the hindbrain — the circuits that had been assumed to carry the effect. Fluorescently labelled liraglutide injected peripherally in mice was instead found in the circumventricular organs, and bound neurons in the hypothalamic arcuate nucleus and at other discrete hypothalamic sites. Central uptake required the receptor: no binding was seen in mice lacking GLP-1R ^[3].

Within the arcuate nucleus, the compound was internalised specifically in neurons expressing proopiomelanocortin and cocaine- and amphetamine-regulated transcript. Electrophysiology in murine brain slices showed that GLP-1 stimulates those neurons directly, and inhibits neurons expressing neuropeptide Y and agouti-related peptide indirectly, through GABA-dependent signalling ^[3].

The structure-activity work reported alongside the compound's discovery also rested on animal pharmacokinetics: protraction of action was assessed in animal models across the whole fatty-acid series, and it is that comparison, not any single figure, that identified twelve carbons as the threshold for protracted action ^[1].

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

Other Areas of Liraglutide 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.

Liver histology. LEAN was an investigator-led phase 2 trial at four UK centres, and it is unusual in this family for using paired liver biopsies rather than imaging. 26 participants were randomised to liraglutide 1.8 mg daily and 26 to placebo, with the primary outcome resolution of definite non-alcoholic steatohepatitis with no worsening of fibrosis at 48 weeks, assessed by two independent pathologists. Resolution occurred in 9 of 23 participants (39%) who received liraglutide and underwent end-of-treatment biopsy, against 2 of 22 (9%) on placebo — relative risk 4.3, 95% CI 1.0 to 17.7, p = 0.019. Progression of fibrosis occurred in 2 of 23 (9%) against 8 of 22 (36%), relative risk 0.2, 95% CI 0.1 to 1.0, p = 0.04. Gastrointestinal disorders were reported by 81% of the liraglutide group against 65% of the placebo group, including diarrhoea, constipation, and loss of appetite ^{[6, 11]}. The trial enrolled 52 participants in total and was designed by a single-group method; the authors describe it as warranting longer-term study, not as settling the question.

Head-to-head against exenatide. LEAD-6 randomised adults with inadequately controlled type 2 diabetes on maximally tolerated oral therapy to liraglutide 1.8 mg once daily (n = 233) or exenatide 10 µg twice daily (n = 231) for 26 weeks, open-label, in fifteen countries. Mean glycated haemoglobin fell by 1.12% against 0.79%, an estimated treatment difference of −0.33, 95% CI −0.47 to −0.18, p < 0.0001, and more participants reached a value below 7% (54% against 43%). Fasting plasma glucose fell further with liraglutide, but postprandial glucose control was less effective after breakfast and dinner. Change in body mass was similar between the two. Nausea was less persistent and minor hypoglycaemia less frequent with liraglutide ^{[2, 9]}. The trial was open-label, which matters when the comparators differ in administration frequency.

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, a glycated haemoglobin value in children — 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.

Liraglutide vs Related Compounds

The distinctions between liraglutide and the compounds it is usually set beside are structural and pharmacokinetic, and nothing else is stated here.

Receptor agonism

Liraglutide, semaglutide, dulaglutide, exenatide and lixisenatide are all agonists at GLP-1R alone. Tirzepatide adds GIPR; retatrutide adds GIPR and GCGR.

Backbone origin

Liraglutide, semaglutide and dulaglutide are analogues of human GLP-1. Exenatide and lixisenatide are not — they derive from exendin-4, a lizard peptide, and share only partial identity with the human hormone.

Duration chemistry

Liraglutide uses a sixteen-carbon fatty acid on lysine 26 and reaches a once-daily schedule ^[1]. Semaglutide uses a longer diacid through a hydrophilic linker plus a protected position 8 and reaches once-weekly. Dulaglutide follows a different route entirely, fusing two GLP-1 analogue chains to an immunoglobulin Fc fragment.

Regulatory position

Liraglutide, semaglutide, dulaglutide, exenatide and lixisenatide are or have been active ingredients of approved pharmaceutical products in the United States, in indications specific to each product. 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

Liraglutide is a modified 31-residue peptide. The backbone recorded in the FDA/NCATS Global Substance Registration System under UNII 839I73S42A is HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG.

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

The backbone is nearly native, and this is the exception in its family. Relative to human GLP-1(7-37), the only amino acid change is arginine for lysine at position 34 — a substitution that exists to leave lysine 26 as the single available acylation site. Unlike semaglutide, liraglutide carries no non-standard residue, so every letter in the string above does stand for the residue actually present. That is a genuine difference between the two molecules, not a difference in how their registers are written.

The acylation is absent from the string and is most of the pharmacology. A palmitic acid is attached to the lysine 26 side chain through a glutamic acid spacer. The published structure-activity work identifies fatty-acid chain length as the parameter that sets protraction, and identifies the cost: longer chains protract further and lose potency ^[1]. A bare 31-residue chain of the letters above would be cleared within minutes.

The registers disagree, slightly, on the formula. PubChem compound identifier 16134956 carries C172H265N43O51 at approximately 3751 g/mol; the Global Substance Registration System carries C172H267N43O52 at 3751.202 g/mol. The difference is one water molecule and reflects each register's convention for the C-terminal group rather than a dispute about the structure. Both are shown here. CAS registry number 204656-20-2 is carried by both registers and is consistent across them.

Frequently Asked Questions

Scientific References

1. Knudsen LB, Nielsen PF, Huusfeldt PO, et al.. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration Journal of medicinal chemistry; 2000. PMID 10794683 doi:10.1021/jm9909645
2. Buse JB, Rosenstock J, Sesti G, et al.. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6) Lancet (London, England); 2009. PMID 19515413 doi:10.1016/S0140-6736(09)60659-0
3. Secher A, Jelsing J, Baquero AF, et al.. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss The Journal of clinical investigation; 2014. PMID 25202980 doi:10.1172/JCI75276
4. Pi-Sunyer X, Astrup A, Fujioka K, et al.. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management The New England journal of medicine; 2015. PMID 26132939 doi:10.1056/NEJMoa1411892
5. Davies MJ, Bergenstal R, Bode B, et al.. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial JAMA; 2015. PMID 26284720 doi:10.1001/jama.2015.9676
6. Armstrong MJ, Gaunt P, Aithal GP, et al.. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study Lancet (London, England); 2016. PMID 26608256 doi:10.1016/S0140-6736(15)00803-X
7. Marso SP, Daniels GH, Brown-Frandsen K, et al.. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes The New England journal of medicine; 2016. PMID 27295427 doi:10.1056/NEJMoa1603827
8. Tamborlane WV, Barrientos-Pérez M, Fainberg U, et al.. Liraglutide in Children and Adolescents with Type 2 Diabetes The New England journal of medicine; 2019. PMID 31034184 doi:10.1056/NEJMoa1903822
9. Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes 2007. NCT00518882
10. Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results 2010. NCT01179048
11. Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis 2010. NCT01237119
12. Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: SCALE™ - Obesity and Pre-diabetes 2011. NCT01272219
13. Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: SCALE™ - Diabetes 2011. NCT01272232
14. Efficacy and Safety of Liraglutide in Combination With Metformin Compared to Metformin Alone, in Children and Adolescents With Type 2 Diabetes 2012. NCT01541215

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.