What is the recommended use and dosage of Trulicity (dulaglutide) for patients with type 2 diabetes?

Trulicity (Dulaglutide) for Type 2 Diabetes

Recommended Dosing

For adults with type 2 diabetes, start Trulicity at 0.75 mg subcutaneously once weekly, then increase to 1.5 mg weekly for additional glycemic control, with further dose escalations in 1.5 mg increments every 4 weeks up to a maximum of 4.5 mg weekly. 1

Adult Dosing Algorithm

• Starting dose: 0.75 mg subcutaneously once weekly 1
• Standard therapeutic dose: Increase to 1.5 mg once weekly for additional glycemic control 1
• Dose escalation: If further glycemic control is needed, increase in 1.5 mg increments (to 3 mg, then 4.5 mg) after at least 4 weeks on current dose 1
• Maximum dose: 4.5 mg once weekly 1

Pediatric Dosing (≥10 years old)

• Starting dose: 0.75 mg subcutaneously once weekly 1
• Maximum dose: 1.5 mg once weekly (after at least 4 weeks on 0.75 mg if additional control needed) 1

Primary Clinical Indications

Trulicity should be prioritized in patients with type 2 diabetes who have established atherosclerotic cardiovascular disease or multiple cardiovascular risk factors, as GLP-1 receptor agonists provide the strongest evidence for reducing major adverse cardiovascular events (MACE). 2

Cardiovascular Disease Indication

• Established ASCVD: Use Trulicity in patients with prior myocardial infarction, ischemic stroke, unstable angina with ECG changes, myocardial ischemia on imaging/stress test, or revascularization of coronary, carotid, or peripheral arteries 2
• High cardiovascular risk without established CVD: Consider Trulicity in patients ≥55 years old with coronary, carotid, or lower extremity artery stenosis >50%, left ventricular hypertrophy, eGFR <60 mL/min/1.73 m², or albuminuria 2
• REWIND trial data: Dulaglutide reduced MACE with a hazard ratio of 0.88 (95% CI 0.79-0.99) over median 5.4 years follow-up, including 68.5% of patients without prior established CVD 2

Chronic Kidney Disease Indication

• No dose adjustment required: Dulaglutide can be used across all stages of CKD without dose modification 2
• Renal benefits: GLP-1 receptor agonists including dulaglutide reduce albuminuria and slow eGFR decline 2
• Preferred in CKD: Consider dulaglutide as an alternative to medications requiring dose adjustment in renal impairment 3, 4

Administration Instructions

Administer Trulicity subcutaneously once weekly at any time of day, with or without food, rotating injection sites between abdomen, thigh, or upper arm. 1

Key Administration Points

• Injection sites: Abdomen, thigh, or upper arm—rotate with each dose 1
• Timing flexibility: Any time of day, with or without food 1
• Visual inspection: Solution should be clear and colorless; do not use if particulate matter or discoloration present 1
• With insulin: Administer as separate injections, never mix; can inject in same body region but not adjacent to each other 1

Missed Dose Management

• ≥3 days until next dose: Administer missed dose as soon as possible 1
• <3 days until next dose: Skip missed dose and resume regular schedule 1
• Day change: Can change weekly administration day if last dose was ≥3 days prior 1

Critical Safety Considerations

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC) 1
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
• Serious hypersensitivity reaction to dulaglutide or any component (including anaphylaxis, angioedema) 1

Important Warnings

• Thyroid C-cell tumors: Dulaglutide causes dose-related thyroid C-cell tumors in rats; counsel patients on symptoms of thyroid tumors (neck mass, dysphagia, dyspnea, persistent hoarseness) 1
• Pancreatitis history: Has not been studied in patients with prior pancreatitis; consider alternative therapies 1, 5
• Severe gastroparesis: Not recommended in patients with severe gastrointestinal disease including severe gastroparesis 1

Common Adverse Effects

• Gastrointestinal effects: Nausea, vomiting, and diarrhea are most frequent, typically transient and mild to moderate 6, 7, 8
• Hypoglycemia risk: Low inherent risk when used alone; monitor when combined with insulin or sulfonylureas 6, 9
• Weight effects: Dulaglutide 1.5 mg consistently produces modest weight loss (up to 3 kg) 6, 7

Clinical Efficacy

Dulaglutide 1.5 mg once weekly demonstrates superior HbA1c reduction compared to metformin, sitagliptin, exenatide twice daily, and insulin glargine, with reductions up to 1.59%. 6, 8, 9

Comparative Effectiveness

• vs. Liraglutide: Non-inferior to liraglutide 1.8 mg daily 6, 8, 9
• vs. Metformin: Significantly more effective than metformin monotherapy 6
• vs. Sitagliptin: Superior to sitagliptin 100 mg daily 6, 8, 9
• vs. Exenatide: Superior to exenatide twice daily 6, 8, 9
• vs. Insulin glargine: Superior to insulin glargine in two trials 6, 9

Long-term Outcomes

• Sustained control: Improvements in glycemic control and weight maintained up to 2 years 6
• Composite endpoint: More patients achieved HbA1c <7.0% with no hypoglycemia, no severe hypoglycemia, and no weight gain compared to metformin, sitagliptin, exenatide, or insulin glargine 9

Decision-Making Independent of HbA1c

In high-risk patients with established type 2 diabetes, the decision to use Trulicity for cardiovascular or renal protection should be made independently of baseline HbA1c or individualized HbA1c target. 2

This reflects the paradigm shift where GLP-1 receptor agonists like dulaglutide are selected for their cardiovascular and renal benefits rather than solely for glycemic control 2.