How do you up-titrate Trulicity (dulaglutide)?

How to Up-Titrate Trulicity (Dulaglutide)

Start 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, escalate in 1.5 mg increments (to 3 mg, then 4.5 mg maximum) after at least 4 weeks on each dose. 1

Initial Dosing and Titration Schedule

Adults

• Begin with 0.75 mg subcutaneously once weekly for the first 4 weeks 1
• Increase to 1.5 mg once weekly after the initial 4-week period 1
• If additional glycemic control is required, increase the dose in 1.5 mg increments (to 3 mg, then 4.5 mg) after at least 4 weeks on the current dose 1
• Maximum recommended dose is 4.5 mg once weekly 1

Pediatric Patients (≥10 years old)

• Start with 0.75 mg subcutaneously once weekly 1
• Maximum dose for pediatric patients is 1.5 mg once weekly, achieved after at least 4 weeks on the 0.75 mg dose 1

Rationale for Slow Titration

The gradual dose escalation strategy minimizes gastrointestinal side effects, which are the most common adverse events with GLP-1 receptor agonists 2. The KDIGO 2020 guidelines specifically recommend starting with a low dose of GLP-1 RA and titrating up slowly to reduce nausea, vomiting, and diarrhea 2.

• Gastrointestinal adverse events (nausea, vomiting, diarrhea) are dose-dependent and occur most frequently during dose escalation 3, 4
• Waiting at least 4 weeks between dose increases allows the body to adapt and reduces the incidence of these side effects 1

Special Considerations During Titration

Renal Impairment

• No dose adjustment is required for any level of renal function, including severe CKD (eGFR >15 mL/min/1.73 m²) 2, 5
• Monitor eGFR when initiating or escalating doses, particularly in patients with CKD who report severe gastrointestinal reactions 5

Concomitant Medications

• If the patient is taking insulin or sulfonylureas, consider reducing these medications before or during dulaglutide titration to minimize hypoglycemia risk 2, 6
• The risk of hypoglycemia with dulaglutide alone is low, but increases when combined with insulin secretagogues 2
• Do not use dulaglutide in combination with DPP-4 inhibitors 2

Cardiovascular and Heart Failure Patients

• Dulaglutide is prioritized for patients with established cardiovascular disease or multiple cardiovascular risk factors 2
• In patients with heart failure and low blood pressure, GLP-1 RAs like dulaglutide can be initiated or up-titrated as they have minimal blood pressure-lowering effects 2

Administration Technique

• Administer once weekly on the same day each week, at any time of day, with or without food 1
• Inject subcutaneously in the abdomen, thigh, or upper arm, rotating injection sites with each dose 1
• If a dose is missed, administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose; otherwise, skip and resume the regular schedule 1

Common Pitfalls and How to Avoid Them

Gastrointestinal Intolerance

• If nausea or vomiting occurs, reassure patients that these symptoms typically diminish over time with continued use 6, 3
• Do not advance to the next dose if the patient is experiencing significant gastrointestinal symptoms; remain at the current dose for an additional 4 weeks 2

Perioperative Management

• Consider holding dulaglutide for one week before elective surgery due to delayed gastric emptying, though evidence on aspiration risk remains uncertain 5
• The half-life of dulaglutide is 4.5-4.7 days, which informs the timing of perioperative discontinuation 5

Pancreatitis Risk

• Dulaglutide has not been studied in patients with a history of pancreatitis; consider alternative therapies in this population 1
• Monitor for symptoms of pancreatitis (severe abdominal pain radiating to the back, nausea, vomiting), particularly after dose escalation 7

Contraindications

• Do not use in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
• Avoid in patients with severe hypersensitivity reactions to dulaglutide 1

Monitoring During Titration

• Assess glycemic control (HbA1c) at 12-24 weeks to determine if further dose escalation is needed 3, 8
• Monitor body weight, as dulaglutide 1.5 mg and higher doses consistently produce weight loss 3, 4
• Check for gastrointestinal symptoms at each dose escalation 2, 4
• In patients with CKD, monitor eGFR if severe gastrointestinal reactions occur 5