Can dulaglutide (Trulicity) be prescribed to a patient with hypothyroidism on levothyroxine who has no history of medullary thyroid carcinoma or MEN 2?

Can Trulicity (Dulaglutide) Be Given to Patients with Hypothyroidism?

Yes, dulaglutide (Trulicity) can be safely prescribed to patients with hypothyroidism on levothyroxine, provided they have no personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2). 1

Absolute Contraindications

The only thyroid-related contraindication for dulaglutide is medullary thyroid carcinoma—not hypothyroidism. 1

• Personal or family history of MTC is an absolute contraindication to dulaglutide. 1
• Multiple endocrine neoplasia syndrome type 2 (MEN 2) is an absolute contraindication. 1
• These restrictions stem from rodent studies showing dose-dependent thyroid C-cell tumors with GLP-1 receptor agonists, though human relevance remains uncertain. 2

Hypothyroidism itself—whether primary, secondary, or iatrogenic—does not appear on the contraindication list for dulaglutide. 1

Safety Evidence in Hypothyroid Patients

• Dulaglutide has been studied extensively in patients with type 2 diabetes, many of whom have concurrent hypothyroidism, without specific safety signals related to thyroid dysfunction. 3, 4
• GLP-1 receptors are expressed in the thyroid gland, but this does not translate to clinically meaningful effects on thyroid function in patients with pre-existing hypothyroidism. 2
• A case report documented a patient with pre-existing medullary thyroid carcinoma who showed no calcitonin elevation during 6 months of dulaglutide 2.0 mg treatment, though this patient should never have received the drug given the contraindication. 5

Clinical Management Algorithm

Step 1: Screen for absolute contraindications

• Ask specifically about personal history of any thyroid cancer, particularly medullary type. 1
• Ask about family history of medullary thyroid cancer or MEN 2 syndrome. 1
• If either is present, do not prescribe dulaglutide—choose an alternative agent such as an SGLT2 inhibitor or DPP-4 inhibitor. 6

Step 2: Verify hypothyroidism is adequately treated

• Confirm the patient is on stable levothyroxine replacement with recent TSH in target range. 2
• Dulaglutide does not require dose adjustment based on thyroid status, but optimizing thyroid function before initiating weight-loss or glucose-lowering therapy improves outcomes. 2

Step 3: Initiate dulaglutide using standard dosing

• Start at 0.75 mg subcutaneously once weekly. 3, 4
• Titrate to 1.5 mg once weekly after 4 weeks if additional glycemic control or weight loss is needed. 3, 4
• No dose adjustment is required for hypothyroidism, renal impairment, age, sex, or body weight. 7

Step 4: Monitor thyroid function during treatment

• Recheck TSH at 3 months after initiating dulaglutide, as weight loss may alter levothyroxine requirements. 2
• If TSH becomes elevated, increase levothyroxine dose; if suppressed, reduce levothyroxine dose. 2
• Monitor for signs of thyroid dysfunction (fatigue, weight changes, temperature intolerance) at each follow-up. 2

Common Pitfalls to Avoid

• Do not confuse hypothyroidism with medullary thyroid carcinoma—only MTC is contraindicated, not benign thyroid disorders. 1
• Do not withhold dulaglutide from patients with well-controlled hypothyroidism on levothyroxine—there is no evidence of harm and substantial evidence of benefit for glycemic control and weight loss. 3, 4
• Do not forget to ask about family history of MTC—even if the patient has no personal history, a family history is an absolute contraindication. 1
• Do not assume thyroid nodules are MTC—most thyroid nodules are benign; if nodules are present, obtain calcitonin and thyroid ultrasound before prescribing dulaglutide. 5

Expected Outcomes

• Dulaglutide provides significant HbA1c reductions (1.2–1.5%) and modest weight loss (2–3 kg) in patients with type 2 diabetes. 3, 4
• Gastrointestinal side effects (nausea, vomiting, diarrhea) are common but typically transient and dose-dependent. 3, 4
• Cardiovascular and renal benefits are maintained in patients with hypothyroidism, as thyroid status does not modify dulaglutide's mechanism of action. 2