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

Trulicity (Dulaglutide) for Type 2 Diabetes

Trulicity is 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

Primary Indications

Glycemic Control

• Start with 0.75 mg subcutaneously once weekly, administered at any time of day with or without food 1
• Increase to 1.5 mg once weekly if additional glycemic control is needed after initial dosing period 2, 1
• Inject subcutaneously in the abdomen, thigh, or upper arm 1
• Administer on the same day each week; day can be changed if last dose was ≥3 days prior 1

Cardiovascular Risk Reduction

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 reducing major adverse cardiovascular events (MACE). 2

Dulaglutide can also be considered for high-risk patients without established CVD who are ≥55 years old with: 2, 3

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

Critical Decision Point: When to Use Dulaglutide vs. SGLT2 Inhibitors

Choose dulaglutide (or another GLP-1 RA) when MACE reduction is the primary concern in patients with established atherosclerotic cardiovascular disease 2

Choose SGLT2 inhibitors instead when the patient has: 2

• Heart failure with reduced ejection fraction (EF <45%)
• Chronic kidney disease (eGFR 30-60 mL/min/1.73m² or UACR >30 mg/g, particularly >300 mg/g)
• Primary concern for heart failure hospitalization or CKD progression

The decision to use dulaglutide for cardiovascular or renal protection should be made independently of baseline HbA1c or HbA1c target. 2

Renal Dosing

No dosage adjustments are required for any level of kidney function, making dulaglutide advantageous in diabetic kidney disease 2

Absolute Contraindications

Do not use dulaglutide if the patient has: 1

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

Important Precautions and Relative Contraindications

Avoid or use extreme caution in patients with: 1

• History of pancreatitis (consider alternative therapies; dulaglutide has not been studied in this population) 1, 4
• Severe gastrointestinal disease including severe gastroparesis 1

Exercise caution and monitor closely in patients with: 1

• Current or prior pancreatic problems
• Kidney or liver disease
• Diabetic retinopathy

Common Pitfalls to Avoid

Missed Dose Management

• If ≥3 days (72 hours) until next scheduled dose: Administer missed dose immediately, then resume weekly schedule 1
• If <3 days until next scheduled dose: Skip the missed dose entirely and resume with next regularly scheduled dose 1
• Never administer two doses within 3 days of each other 1

Drug Interactions

• Do not mix dulaglutide with insulin in the same injection 1
• When combining with insulin or sulfonylureas, anticipate increased hypoglycemia risk and adjust doses accordingly 1
• Dulaglutide delays gastric emptying and may affect absorption of oral medications 1

Expected Adverse Effects

Gastrointestinal symptoms (nausea, vomiting, diarrhea) are the most common adverse effects, typically transient and occurring early in treatment 2, 5, 6

Monitor for serious but rare complications: 1

• Thyroid C-cell tumors (counsel on neck lumps, hoarseness, dysphagia, dyspnea)
• Acute pancreatitis (discontinue if suspected)
• Hypersensitivity reactions
• Acute kidney injury
• Diabetic retinopathy complications
• Cholelithiasis/cholecystitis

Efficacy Expectations

Dulaglutide 1.5 mg once weekly demonstrates: 5, 6, 7

• HbA1c reduction of approximately 0.9-1.1% when added to existing therapy
• 53% of patients achieving HbA1c <7.0% at primary endpoints
• Modest weight loss (typically 2-3 kg)
• Low hypoglycemia risk when used without insulin secretagogues
• Improved β-cell function and favorable lipid/blood pressure effects

Dulaglutide 1.5 mg was superior to exenatide twice daily, insulin glargine, metformin, and sitagliptin, and non-inferior to liraglutide 1.8 mg in head-to-head trials. 5, 7

Special Populations

Pregnancy and Lactation: Unknown safety profile; discuss risks/benefits before use 1

Pediatric Use: Approved for children ≥10 years old for glycemic control only (not for cardiovascular risk reduction) 1