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

Trulicity (Dulaglutide) for Type 2 Diabetes

Trulicity is a once-weekly GLP-1 receptor agonist indicated as an adjunct to diet and exercise for glycemic control in adults and children ≥10 years with type 2 diabetes, and to reduce major adverse cardiovascular events in adults with established cardiovascular disease or multiple cardiovascular risk factors. 1

Dosing and Administration

Start with 0.75 mg subcutaneously once weekly, and increase to 1.5 mg once weekly if additional glycemic control is needed after at least 4 weeks. 2, 1 The medication can be administered at any time of day, with or without food, in the abdomen, thigh, or upper arm. 1

• If a dose is missed and ≥3 days (72 hours) remain until the next scheduled dose, administer as soon as possible and resume the usual weekly schedule. 1
• If <3 days remain until the next dose, skip the missed dose and resume with the next regularly scheduled dose. 1
• Do not mix Trulicity with insulin in the same injection. 1

Patient Selection Based on Cardiovascular Risk

High-Priority Candidates (Proven Mortality/Morbidity Benefit)

For patients with type 2 diabetes and 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 provide the greatest level of evidence for MACE reduction. 2

• The decision to initiate dulaglutide should be made independently of baseline HbA1c or individualized HbA1c target in these high-risk patients. 2
• Dulaglutide demonstrated a hazard ratio of 0.88 (95% CI 0.79-0.99) for MACE reduction in the REWIND trial. 2

Extended Indications for High-Risk Patients Without Established CVD

Dulaglutide can also be considered in patients without established CVD but with high-risk indicators: 2, 3

• Age ≥55 years with coronary, carotid, or lower extremity artery stenosis >50%
• Left ventricular hypertrophy
• eGFR <60 mL/min/1.73m²
• Albuminuria (UACR ≥30 mg/g)

Use in Chronic Kidney Disease

Dulaglutide requires no dose adjustment regardless of kidney function and can be used in patients with eGFR as low as 2 mL/min/1.73m². 2, 4 This makes it particularly advantageous in diabetic kidney disease, where it is generally preferred when additional glycemic therapy is required beyond metformin and SGLT2 inhibitors. 2

Combination Therapy Considerations

With DPP-4 Inhibitors

Discontinue DPP-4 inhibitors (such as sitagliptin) before starting dulaglutide, as the GLP-1 agonist provides superior glycemic control and cardiovascular benefits. 4 Both medications work through the incretin pathway, making their combination redundant. 4

With Insulin or Sulfonylureas

When initiating dulaglutide in patients on sulfonylureas or insulin, reduce the sulfonylurea dose by 50% or basal insulin by 20% to prevent hypoglycemia. 4 Dulaglutide has low intrinsic hypoglycemia risk when used alone or with non-insulin-secretagogue therapy. 5

Preferred Over SGLT2 Inhibitors in Specific Contexts

While SGLT2 inhibitors have the greatest evidence for benefit in heart failure with reduced ejection fraction (EF <45%) or advanced CKD, dulaglutide is preferred when MACE reduction is the primary concern in patients with established atherosclerotic disease. 2

Safety Profile and Contraindications

Absolute Contraindications

Do not use dulaglutide in patients with: 1

• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• History of serious allergic reaction to dulaglutide

Relative Contraindications and Cautions

Dulaglutide has not been studied in patients with a history of pancreatitis; consider other antidiabetic therapies in these patients. 1 The medication is not recommended in patients with severe gastrointestinal disease, including severe gastroparesis. 1

• Use with caution in patients with a history of pancreatitis. 4
• Monitor for symptoms of thyroid tumors (neck lump, hoarseness, dysphagia, dyspnea). 1
• Inform patients about potential risk for cholelithiasis or cholecystitis. 1

Common Adverse Effects

The most frequently reported adverse events are gastrointestinal, including nausea, vomiting, and diarrhea, which are typically transient and mild. 5, 6 Start at the lowest dose (0.75 mg weekly) and titrate slowly to mitigate these symptoms. 4

• Gastrointestinal symptoms occur mainly in the initial stage of treatment and gradually diminish over time. 2
• Incidence of anti-drug antibody formation is low (1-2.8%) with rare injection site reactions. 5

Pediatric Use

Dulaglutide is approved for use in pediatric patients ≥10 years of age with type 2 diabetes as an adjunct to diet and exercise. 1 It is not known if dulaglutide is safe and effective in children under 10 years of age. 1

Pregnancy and Breastfeeding

It is not known if dulaglutide will harm an unborn baby; inform your healthcare provider if you become pregnant while using dulaglutide. 1 It is also not known if dulaglutide passes into breast milk, and the decision to breastfeed should be made in consultation with a healthcare provider. 1