Dulaglutide

Chemical Identity

Property	Value
Molecular Weight	~59.7 kDa
CAS Number	923950-08-7
Peptide Class	GLP-1 Receptor Agonist (Fc Fusion)
Structure	GLP-1(7-37) analog fused to IgG4 Fc
Route	SC injection

Structure

Dulaglutide (Trulicity) consists of two modified GLP-1(7-37) sequences covalently linked to a modified human IgG4 Fc fragment via a small peptide linker. The GLP-1 sequence contains an Aib (aminoisobutyric acid) substitution at position 8 to resist DPP-4 degradation. The Fc fusion provides extended half-life through FcRn recycling.

Mechanism of Action

Dulaglutide activates GLP-1 receptors on pancreatic beta cells, enhancing glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting satiety. The Fc fusion provides a 5-day half-life, supporting once-weekly dosing with minimal peak-to-trough fluctuation.

Clinical Applications

• Type 2 diabetes: Glycemic control (Trulicity)
• Cardiovascular risk reduction: REWIND trial showed CV benefit
• Weight management: Mean weight loss of 3-5 kg
• First-line therapy: Approved for initial therapy with metformin

Pharmacokinetics

• Half-life: 5 days
• Tmax: 48 hours
• Bioavailability: 47-65%
• Metabolism: Proteolytic degradation
• Dosing: 0.75-4.5 mg SC once weekly
• Route: SC injection (abdomen, thigh, upper arm)

Safety and Side Effects

Nausea (13-20%), diarrhea (9-14%), vomiting (6-10%), abdominal pain, decreased appetite, and injection site reactions. Contraindicated in MTC or MEN2 history. Thyroid C-cell tumors in rodents.

References

• Dungan, K.M., et al. (2014). AWARD-5: dulaglutide versus sitagliptin. Lancet Diabetes & Endocrinology, 2, 861-870.
• Gerstein, H.C., et al. (2019). REWIND: dulaglutide and cardiovascular outcomes. New England Journal of Medicine, 381, 221-231.