What are the indications, recommended dosing, contraindications, and common adverse effects of Trulicity (dulaglutide) for adults with type 2 diabetes mellitus?

Trulicity (Dulaglutide) for Type 2 Diabetes Mellitus

Indications

Trulicity is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10 years of age with type 2 diabetes mellitus, and to reduce major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. 1

• Trulicity is specifically recommended for patients with type 2 diabetes and established atherosclerotic cardiovascular disease or chronic kidney disease, where it provides cardiovascular and renal protective benefits beyond glycemic control 2
• The medication reduces major adverse cardiovascular events by approximately 20-26%, including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke 2
• Trulicity requires no dose adjustment across all stages of chronic kidney disease, including patients with eGFR <30 mL/min/1.73 m², making it a preferred agent for patients with renal impairment 2, 3
• It is not indicated for type 1 diabetes mellitus 1
• Trulicity has not been studied in patients with a history of pancreatitis; consider alternative antidiabetic therapies in these patients 1

---

Recommended Dosing and Administration

The recommended starting dose of Trulicity is 0.75 mg subcutaneously once weekly, which can be increased to 1.5 mg once weekly after 4 weeks if additional glycemic control is needed. 4, 5

Standard Titration Schedule:

• Initial dose: 0.75 mg subcutaneously once weekly 4, 5
• Maintenance dose: 1.5 mg once weekly after 4 weeks if tolerated and additional glycemic control is required 4, 5
• Higher doses: In clinical trials, doses of 3 mg and 4.5 mg once weekly have been studied and show greater efficacy, though these are not yet widely approved 1

Administration Details:

• Administer subcutaneously once weekly on the same day each week, at any time of day, with or without meals 5
• Inject in the abdomen, thigh, or upper arm 5
• If a dose is missed, administer as soon as possible if ≤4 days since the missed dose; if >4 days, skip and resume at the next scheduled dose 4

Special Populations:

• Renal impairment: No dose adjustment required for any degree of renal impairment, including end-stage renal disease 2, 3, 4
• Hepatic impairment: No specific dose adjustment recommendations are provided in the FDA label 1
• Pediatric patients ≥10 years: Same dosing as adults 1

---

Contraindications

Trulicity is absolutely contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2). 1

Absolute Contraindications:

• 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

Relative Cautions and Limitations:

• Not recommended in patients with severe gastrointestinal disease, including severe gastroparesis 1
• History of pancreatitis is a relative caution; Trulicity has not been studied in these patients, and alternative therapies should be considered 1
• Use with caution in patients with renal impairment or low systolic blood pressure, those on diuretics, or the elderly, due to potential intravascular volume contraction 2

---

Common Adverse Effects

The most frequently reported adverse effects of Trulicity are gastrointestinal, including nausea (12-21%), diarrhea (9-13%), and vomiting (6-13%), which are typically mild to moderate and transient. 1, 6, 7

Gastrointestinal Effects:

• Nausea: Occurs in 12.4% (0.75 mg) to 21.1% (1.5 mg) of patients 1
• Diarrhea: Occurs in 8.9% (0.75 mg) to 12.6% (1.5 mg) of patients 1
• Vomiting: Occurs in 6.0% (0.75 mg) to 12.7% (1.5 mg) of patients 1
• Abdominal pain: Occurs in 6.5% (0.75 mg) to 9.4% (1.5 mg) of patients 1
• Decreased appetite: Occurs in 4.9% (0.75 mg) to 8.6% (1.5 mg) of patients 1
• Most GI adverse reactions are graded as mild (48-58%) or moderate (35-42%), with severe reactions occurring in 7-11% of cases 1
• GI symptoms typically decrease over time with continued exposure 6, 7

Hypoglycemia:

• Trulicity has a low inherent risk of hypoglycemia when used as monotherapy or with non-insulin-secretagogue therapy 5, 7
• Hypoglycemia risk increases significantly when combined with sulfonylureas or insulin 1, 7
• In combination with sulfonylureas, hypoglycemia (glucose <54 mg/dL) occurred in 20-21% of patients over 78 weeks 1
• In combination with prandial insulin, hypoglycemia occurred in 69-77% of patients over 52 weeks, with severe hypoglycemia in 2.7-3.4% 1

Other Adverse Effects:

• Fatigue: Occurs in 4.2% (0.75 mg) to 5.6% (1.5 mg) of patients 1
• Dyspepsia: Occurs in 4.1% (0.75 mg) to 5.8% (1.5 mg) of patients 1
• Cholelithiasis and cholecystitis: Serious events of acute cholecystitis were reported in 0.5% of Trulicity-treated patients in cardiovascular outcomes trials 1
• Injection site reactions: Rare, with antidrug antibody formation occurring in 1-2.8% of patients 7

Serious Adverse Events:

• Pancreatitis: Although causality has not been definitively established, pancreatitis has been reported in clinical trials and post-marketing surveillance 1, 8
• Discontinue Trulicity if pancreatitis is suspected and do not restart if pancreatitis is confirmed 1

---

Clinical Considerations and Monitoring

Concomitant Medication Adjustments:

• Sulfonylureas: Reduce dose by approximately 50% or discontinue when initiating Trulicity to prevent hypoglycemia 1, 7
• Insulin: Reduce basal insulin dose by approximately 20% when starting Trulicity to minimize hypoglycemia risk 1

Monitoring:

• Assess patients every 4 weeks during dose escalation for gastrointestinal tolerance, weight loss progress, and blood pressure 4
• After reaching therapeutic dose, monitor at least every 3 months for HbA1c, weight, blood pressure, and cardiovascular risk factors 4
• Evaluate treatment response at 12-16 weeks on the maximum tolerated dose 4

Weight Loss:

• Trulicity 1.5 mg once weekly is associated with consistent reductions in body weight, though weight loss is more modest compared to higher-dose GLP-1 receptor agonists like semaglutide 2.4 mg 5, 7

---

Common Pitfalls to Avoid

• Do not delay GLP-1 receptor agonist initiation until multiple oral agents have failed; early use in appropriate candidates (established cardiovascular disease, chronic kidney disease, obesity) yields better outcomes 2
• Do not discontinue metformin when starting Trulicity unless a specific contraindication exists 2
• Do not overlook the need to reduce or stop sulfonylureas, as their combination with Trulicity markedly increases hypoglycemia risk 1, 7
• Do not assume renal dose adjustment is necessary; Trulicity dosing remains unchanged across all CKD stages 2, 3, 4
• Do not prescribe Trulicity to patients with a personal or family history of medullary thyroid carcinoma or MEN 2—these are absolute contraindications 1