Dulaglutide
Dulaglutide is a long-acting GLP-1 receptor agonist administered once weekly by subcutaneous injection. It is used in adults with type 2 diabetes to improve glycaemic control and to reduce major cardiovascular events.
- Chemical formula
- C2646H4044N704O836S18 (approx.)
- CAS number
- 923950-08-7
- ATC code
- A10BJ05
- Molecular weight
- ~63 kDa
- Drug class
- GLP-1 receptor agonist
- Also known as
- LY2189265, Dulaglutida
What is it?
Dulaglutide is a recombinant fusion protein formed by two GLP-1 analogue peptides covalently linked to a modified human IgG4 Fc fragment. The Fc component reduces proteolytic clearance and renal filtration, prolonging the half-life to approximately five days and supporting once-weekly subcutaneous administration. It was developed by Eli Lilly and approved for type 2 diabetes in 2014. Subsequent trials supported a label extension for cardiovascular risk reduction in adults with type 2 diabetes.
Mechanism of action
Dulaglutide activates the GLP-1 receptor in pancreatic beta cells, stimulating glucose-dependent insulin secretion and suppressing inappropriate glucagon release from alpha cells. Receptor activation in the central nervous system reduces appetite, while peripheral signalling slows gastric emptying. The combined effect lowers post-prandial and fasting glucose and produces moderate weight reduction, without intrinsic hypoglycaemia risk in monotherapy. The mechanism is shared by other GLP-1 receptor agonists but differs in pharmacokinetics and dosing convenience.
Pharmacokinetics
After subcutaneous administration, peak plasma concentrations are reached after approximately 24 to 72 hours. Absolute bioavailability is around 47% to 65%. The terminal half-life is about 4.7 to 5.5 days, supporting weekly dosing. Distribution is mostly limited to the vascular compartment, and clearance occurs through general protein catabolism. Mild to moderate renal or hepatic impairment does not require dose adjustment, but dulaglutide has not been extensively studied in severe impairment.
Indications
The medication is approved in adults with type 2 diabetes mellitus, as monotherapy when metformin is inappropriate or as add-on therapy to other antidiabetics, to improve glycaemic control. A second indication, in some markets, is the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple risk factors. According to the prescribing information, treatment must be initiated and supervised by a qualified clinician.
Safety profile
The most common adverse effects are gastrointestinal: nausea, diarrhoea, vomiting and abdominal pain, usually mild to moderate and decreasing over the first weeks of treatment. Acute pancreatitis, gallbladder disease and injection-site reactions have been reported. Hypoglycaemia is rare in monotherapy but can occur in combination with insulin or sulfonylureas. The product carries a boxed warning regarding thyroid C-cell tumours observed in rodents; medullary thyroid carcinoma and multiple endocrine neoplasia type 2 are contraindications, as is severe gastroparesis.
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Frequently asked questions
How is dulaglutide different from semaglutide? ▾
Both are once-weekly GLP-1 receptor agonists used in type 2 diabetes, but their structures differ: dulaglutide is a peptide-Fc fusion protein, while semaglutide is a modified peptide bound to albumin via a fatty diacid linker. Direct head-to-head trials suggest semaglutide produces somewhat greater glycaemic and weight reduction at higher doses, while dulaglutide is generally well tolerated and convenient. The choice between them is made by the prescriber based on individual response and clinical goals.
Does dulaglutide need to be refrigerated? ▾
Yes. According to the prescribing information, dulaglutide pens should be stored in a refrigerator between 2°C and 8°C. After first use, or for travel, the pen can be kept at room temperature below 30°C for a limited period defined in the leaflet, after which it should be discarded. Freezing damages the molecule. Cold-chain integrity is one reason regulatory agencies caution against purchasing GLP-1 agonists from unverified online sources.
Can dulaglutide be used during pregnancy? ▾
Dulaglutide is not recommended during pregnancy. Animal studies suggest potential reproductive risks, and the molecule's long half-life means measurable concentrations persist for weeks after the last dose. Women of reproductive potential should discuss contraception and a planned pregnancy with their clinician, who may switch to insulin therapy when appropriate. According to the prescribing information, breastfeeding while on dulaglutide should also be discussed individually.
Does dulaglutide help with weight loss? ▾
Dulaglutide produces moderate weight reduction in many adults with type 2 diabetes, typically less than seen with high-dose semaglutide or tirzepatide. It is not approved as a weight-management product on its own, although weight reduction is recognised as a beneficial side effect. According to international guidelines, GLP-1 receptor agonists can be considered in adults with type 2 diabetes when both glycaemic control and weight reduction are desired.
What are the main contraindications for dulaglutide? ▾
Personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2 and known hypersensitivity to dulaglutide are formal contraindications. Caution is required in patients with previous pancreatitis, severe gastroparesis or active gallbladder disease, and during pregnancy and breastfeeding. According to the prescribing information, the medical history and current medication list must be reviewed by a clinician before any prescription.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.