Dulaglutide (Trulicity) for Type 2 Diabetes — Weight & Metabolism
Once-weekly GLP-1 receptor agonist for type 2 diabetes with proven cardiovascular benefit and simple auto-injector delivery.
Overview
Dulaglutide is a once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes management with a convenient single-use auto-injector pen. The REWIND trial (n=9,901, median 5.4 years follow-up) demonstrated a 12% reduction in MACE (major adverse cardiovascular events) including CV death, non-fatal MI, and non-fatal stroke (HR 0.88, 95% CI 0.79-0.99, p=0.026), notably in a population with majority primary prevention (69% without established CVD). The AWARD clinical trial program (AWARD-1 through AWARD-11) demonstrated HbA1c reductions of 1.1-1.6% across various comparator trials. Weight loss of 2-5 kg observed across trials. Dulaglutide 4.5mg (highest approved dose) provides additional glycemic benefit. PMID: 31189511, 26666776, 25972482.
Indications
- Type 2 diabetes mellitus as adjunct to diet and exercise
- Cardiovascular risk reduction in adults with T2DM and established CVD or multiple CV risk factors
- Second-line therapy after metformin failure or as add-on to basal insulin
Mechanism of Action
Progressive beta-cell dysfunction and insulin resistance lead to hyperglycemia and cardiovascular risk
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Dulaglutide | 0.75 mg | Once weekly | Initial dose; provides meaningful HbA1c reduction with lower GI side effect rate |
| Dulaglutide | 1.5 mg | Once weekly | Most commonly prescribed dose; HbA1c reduction ~1.3-1.6% |
| Dulaglutide | 3.0 mg | Once weekly | Escalation dose for additional glycemic control if needed after >=4 weeks on 1.5mg |
| Dulaglutide | 4.5 mg | Once weekly | Maximum approved dose; additional 0.2-0.3% HbA1c reduction vs 1.5mg |
Evidence Grade
GRADE A
Safety & Contraindications
- FDA-approved since 2014 with extensive real-world safety data
- Black box warning: thyroid C-cell tumors in rodents; contraindicated with MTC/MEN2 history
- Common GI side effects: nausea (12-21%), diarrhea (8-13%), vomiting (6-13%) - dose-dependent
- Risk of pancreatitis: discontinue promptly if suspected
- Injection site reactions occur in 0.5-1.5% of patients
- Not recommended as first-line therapy for type 1 diabetes or diabetic ketoacidosis