Dulaglutide (Trulicity) is a human GLP-1 receptor agonist approved by the FDA on September 18, 2014. It is a once-weekly injectable medication for type 2 diabetes with significant cardiovascular benefits.
Structure
Dulaglutide is a fusion protein with two identical chains, each containing:
- An N-terminal GLP-1 analog sequence (90% homology to human GLP-1)
- Covalently linked to the Fc portion of a human IgG4 heavy chain
Mechanism of Action
- Glucose-dependent insulin secretion
- Glucagon suppression
- Gastric emptying delay
- Appetite reduction
- Low hypoglycemia risk
The REWIND Trial
- Patients: 9,901 with type 2 diabetes and cardiovascular risk
- Follow-up: Median 5.4 years
- Primary outcome: 12.0% vs 13.4% placebo (HR 0.88, p=0.026)
- Notable: 68.5% of participants had NO pre-existing CVD
Additional Findings:
- 9% reduction in atherosclerosis index
- First evidence of reduced cognitive impairment with a GLP-1 agonist
Clinical Use
- Starting dose: 0.75mg SC once weekly
- Maintenance: 1.5mg once weekly
- Maximum: 4.5mg once weekly
Safety
Common side effects: nausea, diarrhea, vomiting. Black box warning for thyroid C-cell tumors. Contraindicated in MTC or MEN 2 history.