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

Trulicity (Dulaglutide) for Type 2 Diabetes

Trulicity is a once-weekly GLP-1 receptor agonist that should be strongly considered for patients with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors, as it reduces major adverse cardiovascular events and provides effective glycemic control without requiring dose adjustment for renal impairment. 1

Recommended Dosing

Adults

• Starting dose: 0.75 mg subcutaneously once weekly 2
• Standard therapeutic dose: 1.5 mg once weekly for additional glycemic control 2
• Dose escalation: Increase in 1.5 mg increments after at least 4 weeks on current dose if additional glycemic control needed 2
• Maximum dose: 4.5 mg once weekly 2

Pediatric Patients (≥10 years)

• Starting dose: 0.75 mg once weekly 2
• Maximum dose: 1.5 mg once weekly after at least 4 weeks on 0.75 mg if needed 2

Administration Guidelines

• Inject subcutaneously in abdomen, thigh, or upper arm 2
• Administer any time of day, with or without food 2
• Rotate injection sites with each dose 2
• If a dose is missed, administer as soon as possible only if ≥3 days (72 hours) remain until next scheduled dose; otherwise skip and resume regular schedule 2

Clinical Indications Based on Cardiovascular Risk

Highest Priority Populations

For patients with established atherosclerotic cardiovascular disease (prior MI, ischemic stroke, unstable angina with ECG changes, myocardial ischemia on imaging, or revascularization), GLP-1 receptor agonists like dulaglutide have the strongest evidence for reducing major adverse cardiovascular events (MACE). 1

For high-risk patients without established CVD, dulaglutide should be considered if they are ≥55 years old with any of the following: 1

• Coronary, carotid, or lower extremity artery stenosis >50%
• Left ventricular hypertrophy
• eGFR <60 mL/min/1.73 m²
• Albuminuria

Cardiovascular Outcomes Evidence

The REWIND trial demonstrated that dulaglutide reduced MACE with a hazard ratio of 0.88 (95% CI 0.79,0.99), notably in a population where 68.5% had no prior established cardiovascular disease. 1 This distinguishes dulaglutide from other GLP-1 receptor agonists that primarily showed benefit only in patients with established CVD.

Use in Chronic Kidney Disease

No dose adjustment is required for dulaglutide regardless of renal function. 1 This is a significant advantage over other diabetes medications:

• Safe across all stages of CKD, including patients with eGFR as low as 15 mL/min/1.73 m² 1
• Dulaglutide reduces albuminuria and slows eGFR decline 1
• In a head-to-head trial against insulin glargine in patients with moderate-to-severe CKD (stages G3-G4), dulaglutide produced similar glycemic control but significantly slower GFR decline 1

For patients with CKD requiring additional glucose-lowering beyond metformin and/or SGLT2 inhibitors, adding a long-acting GLP-1 receptor agonist like dulaglutide is preferred. 1

Treatment Decision Algorithm

When to Prioritize Dulaglutide

1. First-line consideration: Type 2 diabetes with established ASCVD where MACE is the primary concern 1
2. Second-line consideration: High cardiovascular risk without established CVD (age ≥55 with risk factors listed above) 1
3. CKD patients: Any stage of CKD requiring GLP-1 therapy, as no dose adjustment needed 1
4. Treatment intensification: Inadequate glycemic control on metformin and/or SGLT2 inhibitors 1

When to Choose SGLT2 Inhibitors Instead

**For patients with heart failure with reduced ejection fraction (EF <45%) or advanced CKD** (eGFR 30-60 mL/min/1.73 m² or UACR >300 mg/g), SGLT2 inhibitors have stronger evidence for reducing heart failure hospitalization and CKD progression. 1 In these populations, SGLT2 inhibitors should be prioritized over GLP-1 receptor agonists.

Treatment Independence from HbA1c

The decision to use dulaglutide for cardiovascular or renal protection should be made independently of baseline HbA1c or individualized HbA1c target in high-risk patients. 1 This means even patients at glycemic goal may benefit from dulaglutide if they have cardiovascular disease or risk factors.

Safety Considerations and Contraindications

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC) 2
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2
• Serious hypersensitivity reaction to dulaglutide or components 2

Important Warnings

Pancreatitis risk: Dulaglutide has not been studied in patients with a history of pancreatitis; consider alternative therapies in these patients. 2 Case reports document acute pancreatitis occurring after dose escalation. 3

Thyroid C-cell tumors: Counsel patients about potential MTC risk and symptoms (neck mass, dysphagia, dyspnea, persistent hoarseness), though routine calcitonin monitoring is of uncertain value. 2

Severe gastrointestinal disease: Not recommended in patients with severe gastroparesis or severe GI disease. 2

Common Adverse Effects

The most frequent adverse events are gastrointestinal (nausea, vomiting, diarrhea), typically mild-to-moderate and decreasing over time. 4, 5 Dulaglutide has a low inherent risk of hypoglycemia when used alone. 4, 5

Clinical Efficacy Data

Dulaglutide 1.5 mg once weekly demonstrated:

• Superiority to placebo, metformin, sitagliptin, exenatide BID, and insulin glargine for HbA1c reduction 5
• Non-inferiority to liraglutide for glycemic control 4, 5
• Mean HbA1c reduction of 1.3% at 6 months and 2.0% at 12 months in real-world practice 6
• Consistent bodyweight reduction (mean 2.0 kg at 6 months, 3.5 kg at 12 months) 6
• Durable glycemic control maintained up to 104 weeks 5

Pharmacokinetic Profile

• Time to maximum concentration: 48 hours 7
• Half-life: 5 days, supporting once-weekly dosing 7
• Steady state: Achieved between 2nd and 4th doses 7
• Low intra-individual variability (<17% CV) 7
• No clinically relevant effects from age, body weight, sex, race, ethnicity, or injection site 7