What are the considerations for using Ozempic (semaglutide) in a patient with a history of thyroid nodules and type 2 diabetes, given the potential increased risk of myocardial infarctions (MIs)?

Ozempic Does NOT Cause Myocardial Infarctions – It Reduces Cardiovascular Risk

Ozempic (semaglutide) does not cause myocardial infarctions; in fact, it significantly reduces the risk of major adverse cardiovascular events, including MI, by 26% in patients with type 2 diabetes and established cardiovascular disease. 1

Evidence for Cardiovascular Protection

The SUSTAIN-6 trial definitively demonstrated that semaglutide reduces cardiovascular risk rather than increasing it 1:

• Primary outcome reduction: The composite of cardiovascular death, nonfatal MI, or nonfatal stroke occurred in 6.6% of semaglutide patients versus 8.9% of placebo patients (HR 0.74,95% CI 0.58-0.95) 1
• Nonfatal MI specifically: Occurred in 2.9% of semaglutide patients versus 3.9% of placebo patients (HR 0.74,95% CI 0.51-1.08) 1
• Nonfatal stroke reduction: 1.6% versus 2.7% (HR 0.61,95% CI 0.38-0.99) 1

The American Diabetes Association and European Society of Cardiology both recommend semaglutide specifically for patients with type 2 diabetes and established cardiovascular disease to reduce cardiovascular events 2, 3.

Considerations for Patients with Thyroid Nodules

The critical concern with thyroid nodules is NOT cardiovascular risk, but rather the contraindication related to thyroid C-cell tumors 4:

• Semaglutide 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) 4
• The presence of benign thyroid nodules alone is not a contraindication, but requires careful evaluation to rule out MTC 4
• Counsel patients about symptoms of thyroid tumors (neck mass, dysphagia, dyspnea, persistent hoarseness) 4

Pre-Treatment Thyroid Assessment Required

Before initiating semaglutide in a patient with thyroid nodules 5:

• Document personal and family history of thyroid cancer, particularly MTC 5
• Measure baseline TSH, T3, T4 to assess thyroid function 5
• Consider calcitonin measurement if there is any suspicion of MTC, though routine monitoring is of uncertain value 4
• Thyroid ultrasound may be warranted to characterize existing nodules 4

Clinical Decision Algorithm

For a patient with type 2 diabetes, thyroid nodules, and cardiovascular risk:

1. First, rule out MTC/MEN 2 through history and appropriate testing 4
2. If benign nodules confirmed: Semaglutide is appropriate and provides cardiovascular benefit 1, 3
3. If MTC/MEN 2 present or suspected: Semaglutide is contraindicated; consider alternative GLP-1 RA or other glucose-lowering agents 4
4. If established cardiovascular disease: Semaglutide is specifically recommended to reduce MI and stroke risk 2, 3, 1

Common Pitfall to Avoid

Do not confuse the thyroid safety concern (C-cell tumors from rodent studies) with cardiovascular risk 4, 1. The cardiovascular data in humans is robust and demonstrates protection, not harm 1. The thyroid concern is specific to a rare cancer type and requires screening, but does not relate to MI risk 4.

Additional Safety Monitoring

Beyond thyroid considerations, monitor for 2, 6:

• Pancreatitis risk: Use with caution in patients with history of pancreatitis 2
• Diabetic retinopathy complications: Semaglutide has been associated with worsening retinopathy, possibly related to rapid glucose reduction 2, 1
• Renal function: No dose adjustment needed, but monitor as semaglutide improves nephropathy outcomes 1

The bottom line: Semaglutide protects against MI rather than causing it, but requires careful thyroid evaluation before initiation in patients with thyroid nodules. 1, 4