What are the indications, starting dose, titration schedule, contraindications, adverse effects, and monitoring recommendations for Trulicity (dulaglutide) in adult patients with type 2 diabetes mellitus?

Trulicity (Dulaglutide) for Type 2 Diabetes Mellitus

Indications

Trulicity is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10 years with type 2 diabetes, and to reduce major adverse cardiovascular events (cardiovascular death, non-fatal MI, or non-fatal stroke) in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. 1

• Trulicity should not be used in patients with type 1 diabetes mellitus 1
• It has not been studied in patients with a history of pancreatitis; consider alternative antidiabetic therapies in these patients 1
• It is not recommended in patients with severe gastrointestinal disease, including severe gastroparesis 1

Starting Dose and Titration Schedule

Adults

The recommended starting dose is 0.75 mg subcutaneously once weekly, with dose escalation to 1.5 mg once weekly for additional glycemic control. 1

• If further glycemic control is needed, increase the dose in 1.5 mg increments after at least 4 weeks on the current dose 1
• The maximum recommended dose is 4.5 mg subcutaneously once weekly 1
• Administer once weekly at any time of day, with or without food 1

Pediatric Patients (≥10 years)

Start with 0.75 mg subcutaneously once weekly, with a maximum dose of 1.5 mg once weekly after at least 4 weeks on the 0.75 mg dose if additional glycemic control is needed. 1

Administration Technique

• Inject subcutaneously in the abdomen, thigh, or upper arm, rotating injection sites with each dose 1
• The solution should appear clear and colorless; do not use if particulate matter or coloration is seen 1
• When using with insulin, administer as separate injections and never mix; injections may be in the same body region but should not be adjacent 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 the missed dose 1

Contraindications

Trulicity is absolutely contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 1

• Serious hypersensitivity reaction to dulaglutide or any product component, including anaphylactic reactions and angioedema 1
• Pregnancy or breastfeeding 2

Adverse Effects

Common Gastrointestinal Effects

The most frequently reported adverse events are gastrointestinal-related: nausea, vomiting, and diarrhea, which are typically transient and generally mild. 3, 4, 5

• These gastrointestinal disturbances are dose-dependent and tend to diminish over time 6
• Nausea can be minimized by gradual dose titration 2

Serious Adverse Effects to Monitor

• Pancreatitis: Discontinue if pancreatitis is suspected and do not restart if confirmed 2, 7
• Hypoglycemia: Risk increases when combined with insulin, sulfonylureas, or glinides 2
• Thyroid C-cell tumors: Counsel patients about potential risk and symptoms (neck mass, dysphagia, dyspnea, persistent hoarseness) 1
• Injection site reactions 2
• Weight loss (typically modest but consistent with the 1.5 mg dose) 4, 5
• Headache, weakness, or dizziness 2

Rare but Serious

• Diabetic retinopathy complications have been reported with GLP-1 receptor agonists, though causality is unclear 2

Monitoring Recommendations

Before Initiation

• Screen for personal or family history of MTC or MEN 2 1
• Assess for history of pancreatitis 1
• Evaluate for severe gastrointestinal disease or gastroparesis 1
• Review concomitant medications, particularly insulin, sulfonylureas, or glinides 2

During Treatment

• Hypoglycemia surveillance: Monitor closely when used with insulin, sulfonylureas, or glinides; consider reducing doses of these agents 2
• Gastrointestinal symptoms: Assess for persistent nausea, vomiting, or abdominal pain that could indicate pancreatitis 2, 7
• Weight: Track bodyweight changes, as consistent reductions are expected with the 1.5 mg dose 4
• Thyroid monitoring: Routine serum calcitonin or thyroid ultrasound is of uncertain value for early MTC detection 1
• Renal function: No dosage adjustments are required for any level of renal impairment 2

Special Precautions

Gastric Emptying

• Dulaglutide may delay gastric emptying; use caution in patients with clinically meaningful gastroparesis or prior gastric surgery, including bariatric surgery 2
• This effect is usually transient with longer-acting GLP-1 receptor agonists 2

Surgical Considerations

• Consider withholding before major surgery or procedures requiring prolonged fasting, though specific guidance is not provided in the dulaglutide label (extrapolated from SGLT2 inhibitor recommendations) 2

Renal Function

No dosage adjustments are required for dulaglutide regardless of renal function, including in patients with eGFR <30 mL/min/1.73 m² or end-stage renal disease. 2

• This represents a significant advantage over some other antidiabetic agents 2
• For patients with eGFR <30 mL/min/1.73 m², GLP-1 receptor agonists like dulaglutide are preferred over SGLT2 inhibitors for additional glucose lowering 2

Common Pitfalls to Avoid

• Do not use dulaglutide in patients with type 1 diabetes 1
• Do not fail to reduce insulin or sulfonylurea doses when initiating dulaglutide, as this increases hypoglycemia risk 2
• Do not restart dulaglutide if pancreatitis is confirmed 2
• Do not use in patients with personal or family history of MTC or MEN 2 1
• Do not assume renal dose adjustment is needed—dulaglutide requires no modification for any level of kidney function 2

Efficacy Summary

• Dulaglutide 1.5 mg once weekly demonstrated superior A1C reduction compared with placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide 3, 5
• It was noninferior to liraglutide 1.8 mg once daily for A1C reduction 4, 6
• A1C reductions ranged from -0.78% to -1.51% across clinical trials 5
• Weight changes ranged from -0.35 kg to -3.03 kg, with consistent reductions observed with the 1.5 mg dose 4, 5
• Improvements in glycemic control and bodyweight were maintained during long-term treatment up to 2 years 4