Dulaglutide
GLP-1 Receptor AgonistapprovedAlso known as: Trulicity, LY2189265
An FDA-approved once-weekly GLP-1 receptor agonist for type 2 diabetes with proven cardiovascular benefits and convenient single-use pen delivery.
Overview
Dulaglutide is a long-acting GLP-1 receptor agonist developed by Eli Lilly, marketed as Trulicity. It consists of a modified GLP-1 analog linked to a modified human IgG4 Fc fragment, which extends its half-life to approximately 5 days, allowing once-weekly dosing. Approved by the FDA in 2014 for type 2 diabetes, dulaglutide became one of the best-selling GLP-1 RAs due to its convenient ready-to-use pen device that requires no mixing or needle handling. The REWIND trial demonstrated cardiovascular benefits even in patients without established cardiovascular disease, broadening its indication. Dulaglutide produces moderate weight loss (3-5 kg) as a secondary benefit.
Mechanism of Action
Dulaglutide activates the GLP-1 receptor through its modified GLP-1 analog component. The IgG4-Fc fusion prevents renal clearance and enables FcRn-mediated recycling, achieving a ~5-day half-life. It enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and activates central satiety centers. The GLP-1 analog portion contains amino acid substitutions that resist DPP-4 degradation while maintaining receptor binding affinity.
Molecular Formula
Fusion protein (~59.7 kDa)
Molecular Weight
59670 g/mol
Sequence
GLP-1(7-37) analog fused to modified human IgG4 Fc fragment via small peptide linker
Dosage Protocols
Dose Range
0.75mg – 4.5mg
Frequency
Once weekly
Route
subcutaneous
Cycle Length
Ongoing / chronic
Start at 0.75mg weekly. May increase to 1.5mg, then 3.0mg, then 4.5mg for additional glycemic control. Same day each week, any time of day, with or without meals.
Source: FDA prescribing information (Trulicity)
Side Effects
| Effect | Severity |
|---|---|
| Nausea | moderate |
| Diarrhea | mild |
| Vomiting | moderate |
| Abdominal pain | mild |
| Decreased appetite | mild |
| Injection site reaction | mild |
| Pancreatitis | severe |
Pros & Cons
Convenient once-weekly dosing with a ready-to-use pen requiring no mixing or visible needle
Proven cardiovascular benefit in REWIND trial, even in patients without established CVD
Effective HbA1c reduction (1.0-1.6%) with moderate weight loss
Well-established long-term safety profile with extensive post-marketing data
Less weight loss compared to semaglutide and tirzepatide
GI side effects common, particularly nausea during initiation
Not specifically approved for weight management (off-label for obesity)
Thyroid C-cell tumor boxed warning based on rodent data
Research Studies
Legal Status
FDA-approved (2014) for type 2 diabetes. Prescription-only. EMA-approved. Widely available globally with insurance coverage for T2DM.
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