Dulaglutide Research, Specifications & Scientific Information

Introduction

Dulaglutide is the odd one out in this category, and the reason is size. Every other GLP-1 receptor agonist described in this library is a peptide of thirty or forty residues, given duration by a fatty acid that binds serum albumin. Dulaglutide is a 59.7 kDa recombinant protein: two identical chains, each joining a modified GLP-1 analogue to an immunoglobulin G4 Fc fragment through a flexible linker, disulfide-bonded into a homodimer ^[1]. It reaches a once-weekly schedule not by borrowing albumin's residence time but by being built onto an antibody fragment that already has one.

That engineering choice has a consequence worth stating at the outset, because it separates this entry from the others around it: dulaglutide is not a synthetic peptide and cannot be made by solid-phase synthesis. It is expressed in cells.

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

Dulaglutide is a recombinant fusion protein developed by Eli Lilly and Company under the code LY2189265 and first characterised in the peer-reviewed literature in 2010 ^[1].

Its regulatory position needs two sentences rather than one.

It is an approved active ingredient. Dulaglutide is the active ingredient of a finished pharmaceutical product that holds U.S. Food and Drug Administration approval.

The approval belongs to that finished product. 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 substance in the abstract. Nothing about that approval extends to research-grade material supplied for laboratory use, whatever the molecule written on the label.

Functionally, dulaglutide is a single-receptor agonist: one target, the GLP-1 receptor. Structurally it belongs to two families at once — the glucagon–secretin superfamily by virtue of its GLP-1 portion, and the immunoglobulin Fc fusion proteins by virtue of everything else.

Dulaglutide Specifications

Dulaglutide is not a synthetic peptide and is not comparable in scale to the other compounds in this category. The 275-residue string above is ONE of two identical chains recorded for dulaglutide in the FDA/NCATS Global Substance Registration System under UNII WTT295HSY5; the molecule is a disulfide-linked homodimer of that chain, which is why the molecular mass is about sixteen times that of an acylated GLP-1 analogue. Each chain has three parts. The first 31 residues are a GLP-1(7-37) analogue carrying three substitutions relative to the human hormone — glycine for alanine at position 8, glutamic acid for glycine at position 22, and glycine for arginine at position 36. A glycine- and serine-rich linker of fifteen residues follows. The remainder is a modified human immunoglobulin G4 Fc fragment. Unlike the acylated analogues in this family, every modification in dulaglutide is a standard amino acid substitution, so single-letter code expresses the backbone completely; what it does not express is the dimerisation, the disulfide bonding or the glycosylation of the Fc portion. The formula and mass shown are the register's calculated values for the complete protein. 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 Dulaglutide 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 sites in the central nervous system involved in the regulation of food intake. Dulaglutide's GLP-1 portion engages that receptor; the rest of the molecule does not.

The design problem is the familiar one — native GLP-1 is cleared within minutes by dipeptidyl peptidase-4 and by the kidney — and dulaglutide's answer is structural on both counts. The substitution of glycine for alanine at position 8 of the GLP-1 portion removes the dipeptidyl peptidase-4 cleavage site. The Fc fragment defeats renal clearance a different way: at roughly 59.7 kDa the molecule is far too large to be filtered at the glomerulus, and the Fc portion additionally engages the neonatal Fc receptor, the recycling pathway that gives immunoglobulins their long plasma residence.

The price of that approach is the one every large biologic pays. A fusion protein must be expressed in cells, purified as a protein, and characterised as a glycosylated macromolecule rather than as a defined small chemical entity. The additional substitutions in the GLP-1 portion, at positions 22 and 36, were made in that context.

Dulaglutide Mechanism of Action

In vitro research

The characterisation reported with the molecule's description tests the assumption that a fusion of this size could still work as an agonist, which was not obvious: the GLP-1 receptor's binding site accommodates the peptide's N-terminus, and hanging a 50 kDa protein off the other end might reasonably have cost activity.

It did not. In rodent and primate cell systems the fusion protein retained full receptor activity, and in isolated islets it produced insulinotropic activity similar to that of the native peptide ^[1]. That is the central in vitro result: the Fc fragment extends residence time without paying for it at the receptor.

Analytical characterisation of supplied material is a separate exercise from receptor pharmacology. For a molecule of this class it is protein analytics — size-exclusion and reversed-phase chromatography, mass spectrometry of a glycosylated species, and assays for aggregation — rather than the peptide mapping that suffices for a thirty-residue chain.

What Is Dulaglutide Being Researched For?

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

• Type 2 diabetes mellitus in adults — the AWARD programme, including trials against placebo and against two other GLP-1 receptor agonists ^{[2, 3]} and a later trial of an expanded amount range ^[6].
• Cardiovascular outcomes in type 2 diabetes — a trial enrolling participants both with and without previous cardiovascular disease, which is what distinguishes it from most trials of its kind ^[4].
• Renal outcomes in type 2 diabetes — an exploratory analysis within that trial ^[5].
• Type 2 diabetes in children and adolescents — a randomised trial in participants aged ten to under eighteen ^[7].

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 Dulaglutide

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.

REWIND — cardiovascular outcomes in type 2 diabetes

Population. 9,901 participants aged at least 50 with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors, at 371 sites in 24 countries. Mean age 66.2 years, median glycated haemoglobin 7.2%, 46.3% women ^{[4, 9]}.

Endpoint and duration. Primary outcome the first occurrence of a composite of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes, assessed by intention to treat. Median follow-up 5.4 years ^[4].

Result. The primary composite outcome occurred in 594 of 4,949 participants (12.0%) receiving dulaglutide 1.5 mg weekly, an incidence of 2.4 per 100 person-years, against 663 of 4,952 (13.4%) receiving placebo, an incidence of 2.7 per 100 person-years — hazard ratio 0.88, 95% CI 0.79 to 0.99, p = 0.026. All-cause mortality did not differ between groups: 536 (10.8%) against 592 (12.0%), hazard ratio 0.90, 95% CI 0.80 to 1.01, p = 0.067 ^[4].

Adverse events. A gastrointestinal adverse event was reported by 2,347 participants (47.4%) receiving dulaglutide against 1,687 (34.1%) receiving placebo, p < 0.0001 ^[4].

Limitations. The effect estimate sits close to unity and the confidence interval's upper bound is 0.99; all-cause mortality was not significantly different. The population had a median glycated haemoglobin of 7.2%, lower than in most cardiovascular outcome trials in this class, and roughly two-thirds had no previous cardiovascular event — a primary-prevention majority, which is unusual and which the interpretation depends on.

REWIND renal analysis

Population. The same 9,901 participants. At baseline, 791 (7.9%) had macroalbuminuria and mean estimated glomerular filtration rate was 76.9 mL/min per 1.73 m² ^[5].

Endpoint and duration. The renal component of the composite microvascular outcome: first occurrence of new macroalbuminuria, a sustained decline in estimated glomerular filtration rate of 30% or more from baseline, or chronic renal replacement therapy. Median follow-up 5.4 years, comprising 51,820 person-years ^[5].

Result. The renal outcome developed in 848 participants (17.1%) receiving dulaglutide, an incidence of 3.5 per 100 person-years, against 970 (19.6%) receiving placebo, 4.1 per 100 person-years — hazard ratio 0.85, 95% CI 0.77 to 0.93, p = 0.0004. The clearest component was new macroalbuminuria, hazard ratio 0.77, 95% CI 0.68 to 0.87, p < 0.0001; the hazard ratio was 0.89, 95% CI 0.78 to 1.01, p = 0.066 for sustained decline in filtration rate, and 0.75, 95% CI 0.39 to 1.44, p = 0.39 for chronic renal replacement therapy ^[5].

Limitations. Exploratory, and the authors label it so. The composite is driven by its albuminuria component; the two harder components — filtration-rate decline and renal replacement therapy — did not reach significance on their own.

AWARD-6 — head-to-head against liraglutide

Population. 599 adults with inadequately controlled type 2 diabetes on metformin of at least 1,500 mg daily, glycated haemoglobin 7.0% to 10.0%, body-mass index 45 kg/m² or lower, at 62 sites in nine countries ^{[3, 10]}.

Endpoint and duration. Primary outcome non-inferiority, margin 0.4%, of once-weekly dulaglutide 1.5 mg against once-daily liraglutide 1.8 mg for change in glycated haemoglobin at 26 weeks, by intention to treat. Open-label, with four further weeks of safety follow-up ^[3].

Result. Least-squares mean reduction in glycated haemoglobin was 1.42% with dulaglutide and 1.36% with liraglutide, a mean treatment difference of −0.06%, 95% CI −0.19 to 0.07, p < 0.0001 for non-inferiority ^[3].

Adverse events. The most common gastrointestinal events were nausea (20% against 18%), diarrhoea (12% against 12%), dyspepsia (8% against 6%) and vomiting (7% against 8%). Discontinuation for adverse events was 6% in each group. Hypoglycaemia occurred at 0.34 and 0.52 events per participant per year respectively, with no severe hypoglycaemia reported ^[3].

Limitations. Open-label, which is difficult to avoid when comparing a weekly administration with a daily one, and non-inferiority rather than superiority in design. Twenty-six weeks.

AWARD-1 — against placebo and against exenatide

Population. Adults with type 2 diabetes receiving metformin 1,500–3,000 mg and pioglitazone 30–45 mg, randomised 2:2:2:1 to once-weekly dulaglutide 1.5 mg, once-weekly dulaglutide 0.75 mg, exenatide 10 µg twice daily, or placebo. Mean baseline glycated haemoglobin 8.1% ^{[2, 8]}.

Endpoint and duration. Primary objective superiority of dulaglutide 1.5 mg over placebo for change in glycated haemoglobin at 26 weeks, within a 52-week trial; the placebo-controlled period ran to 26 weeks ^[2].

Result. Least-squares mean change in glycated haemoglobin at the primary endpoint was −1.51% for dulaglutide 1.5 mg, −1.30% for dulaglutide 0.75 mg, −0.99% for exenatide and −0.46% for placebo. Both dulaglutide groups were superior to placebo at 26 weeks and to exenatide at 26 and 52 weeks, all adjusted one-sided P < 0.001, and a greater proportion of participants reached glycated haemoglobin targets, all P < 0.001 ^[2].

Adverse events. Total hypoglycaemia incidence at 26 and 52 weeks was lower with dulaglutide 1.5 mg than with exenatide, and no participant receiving dulaglutide reported severe hypoglycaemia. The most common gastrointestinal events were nausea, vomiting and diarrhoea, mostly mild to moderate and transient ^[2].

Limitations. Both comparator arms sit on a background of metformin and pioglitazone, which narrows the population; the exenatide comparison is against the twice-daily product rather than the extended-release one.

AWARD-11 — expanded amount range

Population. 1,842 adults with type 2 diabetes inadequately controlled on metformin. Mean baseline glycated haemoglobin 8.6%, mean body-mass index 34.2 kg/m² ^{[6, 12]}.

Endpoint and duration. Primary objective superiority of once-weekly dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg for reduction in glycated haemoglobin at 36 weeks, within a 52-week trial. Two estimands were prespecified: a treatment-regimen estimand regardless of discontinuation or rescue medication, and an efficacy estimand on treatment without rescue ^[6].

Result. At 36 weeks, 4.5 mg was superior to 1.5 mg on both estimands — treatment-regimen −1.77% against −1.54%, estimated treatment difference −0.24%, P < 0.001; efficacy −1.87% against −1.53%, difference −0.34%, P < 0.001. The 3.0 mg group was superior on the efficacy estimand (difference −0.17%, P = 0.003) but not on the treatment-regimen estimand (difference −0.10%, P = 0.096). Change in body mass at 36 weeks was −4.6 kg against −3.0 kg for 4.5 mg against 1.5 mg, difference −1.6 kg, P < 0.001. Nausea was reported by 13.4%, 15.6% and 16.4% and vomiting by 5.6%, 8.3% and 9.3% across the three groups ^[6].

Limitations. The divergence between the two estimands for the 3.0 mg comparison is the honest finding here: whether that comparison counts as positive depends on which estimand is read, and the trial reports both rather than choosing.

AWARD-PEDS — youths with type 2 diabetes

Population. 154 participants aged ten to under eighteen with type 2 diabetes and body-mass index above the 85th percentile, on lifestyle modification alone or with metformin, with or without basal insulin ^{[7, 11]}.

Endpoint and duration. Primary endpoint the change from baseline in glycated haemoglobin at 26 weeks, in a double-blind placebo-controlled trial randomised 1:1:1, followed by a 26-week open-label extension ^[7].

Result. At 26 weeks, mean glycated haemoglobin had risen by 0.6 percentage points with placebo and fallen by 0.6 and 0.9 percentage points in the 0.75 mg and 1.5 mg groups respectively, P < 0.001 for both against placebo. A glycated haemoglobin below 7.0% was reached by 51% of the pooled dulaglutide groups against 14% of the placebo group, P < 0.001. Fasting glucose rose by 17.1 mg/dL with placebo and fell by 18.9 mg/dL in the pooled dulaglutide groups, P < 0.001. There was no between-group difference in change in body-mass index ^[7].

Adverse events. Gastrointestinal adverse events were more frequent with dulaglutide than with placebo. The safety profile was consistent with that reported in adults ^[7].

Limitations. 154 participants over 26 weeks with an open-label extension. The absence of any effect on body-mass index in this population is a genuine negative result and is reported as such.

Preclinical Research on Dulaglutide

Animal research

The animal work reported with the molecule's characterisation exists to answer one question: whether an Fc fusion actually delivers the residence time the design predicts, and whether the receptor activity survives in a whole animal.

Half-life was 1.5 to 2 days in rats and in cynomolgus monkeys, and serum immunoreactivity representing active compound persisted beyond six days ^[1]. In rats, a single administration enhanced insulin responses during a graded glucose infusion 24 hours later. In diabetic mice, a single administration increased glucose tolerance, and administration twice weekly for four weeks lowered body mass and delayed hyperglycaemia. In monkeys, a single administration significantly increased glucose-dependent insulin secretion for up to a week, and the compound retained its effect when administered once weekly for four weeks ^[1].

The monkey data carry more weight than usual in this instance, and for a specific reason: a fusion protein's pharmacokinetics depend on the neonatal Fc receptor, whose binding differs between species, so rodent residence time alone would have been a weak basis for predicting a weekly human schedule.

Findings described in this section were observed in animals. Nothing in them establishes anything about humans.

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.

Dulaglutide vs Related Compounds

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

Receptor agonism

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

Molecular class

Dulaglutide is a recombinant fusion protein of about 59.7 kDa, expressed in cells. Every other compound in the list above is a synthetic peptide of 4 to 5 kDa. That is a difference in kind, not in degree, and it governs how each is made, purified and characterised.

Duration chemistry

Dulaglutide relies on an immunoglobulin Fc fragment and the recycling pathway that serves it. Liraglutide and semaglutide rely on reversible albumin binding through a fatty acid. Exenatide's extended-release product relies on a microsphere formulation rather than on any modification of the peptide.

Backbone protection

Dulaglutide substitutes glycine for alanine at position 8 of its GLP-1 portion to remove the dipeptidyl peptidase-4 site — a standard residue, expressible in single-letter code. Semaglutide uses a non-standard residue at the same position, which is not.

Regulatory position

Dulaglutide, semaglutide, liraglutide, 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

Dulaglutide is a disulfide-linked homodimer. Each chain is 275 residues, and the sequence recorded in the FDA/NCATS Global Substance Registration System under UNII WTT295HSY5 begins HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGG — the GLP-1 portion — and continues through a glycine- and serine-rich linker into a modified human immunoglobulin G4 Fc fragment.

Three points qualify that record.

The GLP-1 portion carries three substitutions, and all three are standard residues. Against human GLP-1(7-37), the analogue substitutes glycine for alanine at position 8, glutamic acid for glycine at position 22, and glycine for arginine at position 36. Because every one of those is a standard amino acid, single-letter code expresses this backbone completely — which is not true of semaglutide or tirzepatide, whose position-8 residues have no letter. The comparison is worth making precisely because it shows that "the sequence is not the molecule" is a claim about particular molecules rather than a general disclaimer.

What the string still does not express is everything that makes it a protein. The dimerisation, the interchain and intrachain disulfide bonds, and the glycosylation of the Fc portion are all absent from a linear sequence, and all three are part of the material's identity. A synthetic peptide with this sequence would not be dulaglutide.

No PubChem compound identifier resolves. That is expected rather than notable for a glycosylated protein of this size — PubChem's compound records describe defined small molecules — and the field is published as unknown rather than filled. CAS registry number 923950-08-7 and the calculated formula C2646H4034N704O836S18 at approximately 59,700 g/mol are carried by the Global Substance Registration System for the complete protein.

Frequently Asked Questions

Scientific References

1. Glaesner W, Vick AM, Millican R, et al.. Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein Diabetes/metabolism research and reviews; 2010. PMID 20503261 doi:10.1002/dmrr.1080
2. Wysham C, Blevins T, Arakaki R, et al.. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1) Diabetes care; 2014. PMID 24879836 doi:10.2337/dc13-2760
3. Dungan KM, Povedano ST, Forst T, et al.. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial Lancet (London, England); 2014. PMID 25018121 doi:10.1016/S0140-6736(14)60976-4
4. Gerstein HC, Colhoun HM, Dagenais GR, et al.. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial Lancet (London, England); 2019. PMID 31189511 doi:10.1016/S0140-6736(19)31149-3
5. Gerstein HC, Colhoun HM, Dagenais GR, et al.. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial Lancet (London, England); 2019. PMID 31189509 doi:10.1016/S0140-6736(19)31150-X
6. Frias JP, Bonora E, Nevarez Ruiz L, et al.. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11) Diabetes care; 2021. PMID 33397768 doi:10.2337/dc20-1473
7. Arslanian SA, Hannon T, Zeitler P, et al.. Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes The New England journal of medicine; 2022. PMID 35658022 doi:10.1056/NEJMoa2204601
8. A Study in Participants With Type 2 Diabetes Mellitus 2010. NCT01064687
9. Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) 2011. NCT01394952
10. A Study Comparing the Effect of Dulaglutide With Liraglutide in Type 2 Diabetes 2012. NCT01624259
11. A Study of Dulaglutide (LY2189265) in Children and Adolescents With Type 2 Diabetes 2016. NCT02963766
12. A Study of the Efficacy and Safety of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes 2018. NCT03495102

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.