Dulaglutide (Trulicity) Dosing and Treatment Plan for Type 2 Diabetes
Start dulaglutide at 0.75 mg subcutaneously once weekly, then increase to 1.5 mg once weekly for additional glycemic control, with further dose escalation in 1.5 mg increments every 4 weeks as needed up to a maximum of 4.5 mg weekly. 1
Initial Dosing Algorithm
Adults
- Starting dose: 0.75 mg subcutaneously once weekly 1
- Standard therapeutic dose: Increase to 1.5 mg once weekly if additional glycemic control is needed 1
- Dose escalation: If further control required, increase in 1.5 mg increments after at least 4 weeks on current dose 1
- Maximum dose: 4.5 mg once weekly 1
Pediatric Patients (≥10 years)
- 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 1
Administration Details
Inject subcutaneously once weekly at any time of day, with or without food, rotating between abdomen, thigh, or upper arm. 1
- The solution should appear clear and colorless; discard if particulate matter or discoloration is present 1
- When combining with insulin, administer as separate injections in the same body region but not adjacent to each other 1
- If a dose is missed and ≥3 days (72 hours) remain until the next scheduled dose, administer immediately; if <3 days remain, skip the missed dose 1
Clinical Indications Based on Patient Profile
Established Cardiovascular Disease
Dulaglutide is specifically indicated to reduce major adverse cardiovascular events (cardiovascular death, non-fatal MI, or non-fatal stroke) in adults with type 2 diabetes and established CVD or multiple CV risk factors. 1, 2
- Established CVD includes: prior MI, ischemic stroke, unstable angina with ECG changes, myocardial ischemia on imaging/stress test, or revascularization of coronary, carotid, or peripheral arteries 2
- The REWIND trial demonstrated HR 0.88 (95% CI 0.79,0.99) for MACE reduction with dulaglutide 2
High-Risk Primary Prevention
Consider dulaglutide for patients ≥55 years without established CVD but with high-risk indicators: 2
- Coronary, carotid, or lower extremity artery stenosis >50%
- Left ventricular hypertrophy
- eGFR <60 mL/min/1.73 m²
- Albuminuria
The REWIND trial uniquely included 68.5% of patients without prior CVD, demonstrating benefit across both primary and secondary prevention populations 2
Chronic Kidney Disease Considerations
No dose adjustment is required for any level of renal function, making dulaglutide advantageous in CKD. 2
- Dulaglutide requires no dosage adjustments regardless of eGFR 2
- Preferred GLP-1 RA for patients with eGFR <60 mL/min/1.73 m² or UACR ≥30 mg/g who cannot tolerate SGLT2 inhibitors 2
- In the AWARD-7 trial, dulaglutide produced similar glycemic control to insulin glargine but resulted in significantly slower GFR decline in patients with moderate-to-severe CKD 2
Treatment Decision Algorithm
When to Prioritize Dulaglutide Over Other GLP-1 RAs
Choose dulaglutide when MACE reduction is the primary goal, particularly in patients without established CVD but with high-risk features. 2
The level of evidence for MACE benefit in primary prevention is strongest for dulaglutide compared to other GLP-1 RAs, based on the REWIND trial's unique population composition and 5.4-year median follow-up 2
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 benefit than GLP-1 RAs. 2
Combination Therapy
Dulaglutide can be added to SGLT2 inhibitors when glycemic control remains inadequate. 3
- The AWARD-10 trial demonstrated LSM HbA1c reduction of -1.34% with dulaglutide 1.5 mg versus -0.54% with placebo when added to SGLT2 inhibitors 3
- This combination addresses complementary mechanisms: GLP-1 receptor agonism and renal glucose reabsorption inhibition 3
Key Treatment Considerations Independent of HbA1c
The decision to initiate dulaglutide for cardiovascular or renal risk reduction should be made independently of baseline HbA1c or individualized HbA1c target. 2
The REWIND trial showed equivalent MACE reduction above and below median HbA1c of 7.2% (55 mmol/mol), establishing that cardiovascular benefit is not contingent on degree of hyperglycemia 2
Safety Profile and Contraindications
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 1
Common Adverse Effects
- Gastrointestinal symptoms (nausea, vomiting, diarrhea) are most common, typically transient 2, 4, 5
- Nausea occurs in approximately 15% of patients on 1.5 mg dose 3
- Low inherent risk of hypoglycemia when used without insulin or sulfonylureas 4, 5
Important Cautions
- Not studied in patients with severe gastroparesis or severe gastrointestinal disease 1
- Not studied in patients with history of pancreatitis; consider alternative therapies in this population 1
- When combining with insulin or sulfonylureas, reduce doses of these agents by approximately 20% to prevent hypoglycemia 2
Pharmacokinetic Properties Supporting Weekly Dosing
Dulaglutide reaches maximum concentration in 48 hours with a terminal half-life of 5 days, achieving steady state between the second and fourth doses. 6
- Accumulation ratio of 1.56 for the 1.5 mg dose 6
- Intra-individual variability <17% for both AUC and Cmax 6
- No clinically relevant differences based on age, body weight, sex, race, ethnicity, or injection site 6
Expected Clinical Outcomes
Glycemic Control
- HbA1c reductions of 1.2-1.5% from baseline at 26 weeks across clinical trials 4, 5
- Improvements maintained up to 104 weeks 4, 7
- Superior to metformin, sitagliptin, exenatide BID, and insulin glargine; noninferior to liraglutide 4, 7
Weight Effects
- Dulaglutide 1.5 mg consistently produces weight reduction 4
- The 0.75 mg dose shows less consistent weight effects 4