Trulicity (Dulaglutide) Dosing for Type 2 Diabetes
Starting Dose and Standard Titration
Begin dulaglutide at 0.75 mg subcutaneously once weekly, then increase to 1.5 mg once weekly after 4 weeks if additional glycemic control is needed. This two-dose approach is the FDA-approved standard regimen for most patients with type 2 diabetes 1, 2, 3.
The 0.75 mg starting dose minimizes gastrointestinal side effects (nausea, vomiting, diarrhea) that occur in approximately 20% of patients on the 1.5 mg dose 2, 4. After 4 weeks at 0.75 mg, escalate to the 1.5 mg maintenance dose if HbA1c targets are not met and the lower dose is well-tolerated 1, 2.
Higher-Dose Options (Investigational)
For patients requiring more aggressive glycemic control or weight loss, dulaglutide 3.0 mg and 4.5 mg doses have shown superior efficacy in phase 2 trials 5. At 18 weeks, the 3.0 mg dose reduced HbA1c by 1.31% and body weight by 3.9 kg, while the 4.5 mg dose reduced HbA1c by 1.40% and body weight by 4.1 kg, compared to 1.23% and 2.8 kg respectively with the standard 1.5 mg dose 5. However, these higher doses are not yet FDA-approved and should only be used in clinical trial settings.
Administration Details
Inject dulaglutide subcutaneously once weekly in the abdomen, thigh, or upper arm 1. The injection can be given at any time of day, with or without meals 1. The day of weekly administration can be changed if needed, provided at least 3 days (72 hours) have elapsed between doses 1.
Dulaglutide comes in a single-use pen or prefilled syringe that requires no dose preparation or mixing 2, 3.
Renal Impairment: No Dose Adjustment Required
No dose adjustment is necessary for any degree of renal impairment, including patients with eGFR <30 mL/min/1.73 m² or those on dialysis. This is a critical advantage over other GLP-1 receptor agonists like exenatide 1, 6, 7.
In the AWARD-7 trial of 577 patients with moderate-to-severe chronic kidney disease (stages 3-4), dulaglutide 1.5 mg and 0.75 mg demonstrated non-inferior glycemic control compared to insulin glargine, with HbA1c reductions of 1.2% and 1.1% respectively at 26 weeks 7. Importantly, dulaglutide preserved renal function better than insulin, with eGFR at 52 weeks of 34.0 mL/min/1.73 m² (1.5 mg) and 33.8 mL/min/1.73 m² (0.75 mg) versus 31.3 mL/min/1.73 m² with insulin glargine 7.
Monitor eGFR when initiating or escalating doses, particularly in patients with chronic kidney disease who report severe gastrointestinal reactions, as dehydration from nausea/vomiting can precipitate acute kidney injury 6.
Hepatic Impairment: No Dose Adjustment Required
No dose modification is needed for patients with hepatic impairment of any severity 1. Dulaglutide is not primarily cleared by the liver, making it safe across all stages of liver disease 7.
Age Considerations: No Dose Adjustment Required
No dose adjustment is required based on age alone 1. Dulaglutide has been studied in elderly patients without safety concerns beyond the standard adverse event profile 2, 4.
Maximum Dose
The maximum FDA-approved dose is 1.5 mg once weekly 1, 2, 3. Higher doses (3.0 mg and 4.5 mg) remain investigational and are not approved for routine clinical use 5.
Concomitant Medication Adjustments
When starting dulaglutide, reduce or discontinue sulfonylureas to prevent hypoglycemia 1. If the patient is on basal insulin, consider reducing the insulin dose by approximately 20% when initiating dulaglutide, especially if HbA1c is well-controlled at baseline 1.
Discontinue any DPP-4 inhibitors (sitagliptin, linagliptin, etc.) before starting dulaglutide, as concurrent use provides no additional glycemic benefit 1.
Efficacy Expectations
Dulaglutide 1.5 mg once weekly produces HbA1c reductions of approximately 1.1-1.4% from baseline 1, 2, 7, 3. It demonstrates superiority over metformin, sitagliptin, exenatide twice daily, and insulin glargine, and non-inferiority to liraglutide 1.8 mg daily 1, 2, 3.
Weight loss with dulaglutide 1.5 mg averages 2-3 kg over 26-52 weeks 2, 3, 5. The 0.75 mg dose typically does not produce consistent weight reduction 2.
Safety Profile and Monitoring
The most common adverse events are gastrointestinal: nausea (20% with 1.5 mg), diarrhea (17% with 1.5 mg), and vomiting 7, 4. These are typically mild-to-moderate, transient, and decrease over time 4.
Dulaglutide has a low inherent risk of hypoglycemia when used as monotherapy or with metformin 2, 4. In AWARD-7, symptomatic hypoglycemia occurred at a rate of 4.4 events per patient-year with dulaglutide 1.5 mg versus 9.6 events per patient-year with insulin glargine 7.
Monitor for signs of pancreatitis (persistent severe abdominal pain), gallbladder disease, and acute kidney injury secondary to dehydration from gastrointestinal side effects 1, 4.
Absolute Contraindications
Do not prescribe dulaglutide to patients with:
- Personal or family history of medullary thyroid carcinoma 1
- Multiple endocrine neoplasia syndrome type 2 (MEN 2) 1
- History of serious hypersensitivity reaction to dulaglutide 1
Perioperative Considerations
Consider holding dulaglutide for one week (approximately 2 half-lives) before elective surgery due to delayed gastric emptying effects, though evidence on aspiration risk with long-acting GLP-1 receptor agonists remains uncertain 6. The half-life of dulaglutide is 4.5-4.7 days depending on dose 6.
Common Pitfalls to Avoid
- Do not skip the 0.75 mg starting dose in most patients; jumping directly to 1.5 mg increases gastrointestinal side effects and treatment discontinuation 2, 4.
- Do not assume renal dose adjustment is needed; dulaglutide is one of the few GLP-1 receptor agonists safe at all levels of kidney function without modification 1, 6, 7.
- Do not combine with DPP-4 inhibitors; this provides no additional benefit and increases cost 1.
- Do not delay initiation in patients with established cardiovascular disease or chronic kidney disease; dulaglutide reduces major adverse cardiovascular events by approximately 20-26% in these populations 1.