What are the contraindications for Ozempic (semaglutide) in patients with a history of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2, pancreatitis, or impaired renal function?

Contraindications for Ozempic (Semaglutide)

Absolute Contraindications

Ozempic 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), as stated in the FDA boxed warning. 1

• Personal or family history of medullary thyroid carcinoma (MTC): Semaglutide causes thyroid C-cell tumors in rodents, and while human relevance remains undetermined, this represents an absolute contraindication 2, 1

• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2): This autosomal dominant syndrome carries a 70-100% risk of medullary thyroid carcinoma by age 70 years, making semaglutide use contraindicated 2, 1, 3

• Known hypersensitivity to semaglutide or any product components: History of serious hypersensitivity reactions to the drug is an absolute contraindication 2, 1

• Pregnancy and breastfeeding: Ozempic must be discontinued at least 2 months before planned pregnancy due to the long washout period for semaglutide 4, 1

Relative Contraindications and High-Risk Situations Requiring Extreme Caution

History of Pancreatitis

Ozempic has not been studied in patients with a history of pancreatitis, and the FDA label explicitly states to consider another antidiabetic therapy in these patients. 1

• The American College of Cardiology recommends using semaglutide with caution in patients with history of pancreatitis 2
• If pancreatitis is suspected during treatment, discontinue Ozempic promptly and do not restart if pancreatitis is confirmed 1, 5
• Acute pancreatitis has been reported in clinical trials, though causality has not been definitively established 4, 5

Severe Renal Impairment

Unlike exenatide and lixisenatide (which are contraindicated in severe renal impairment/ESRD), semaglutide can be used with caution in patients with severe renal impairment or end-stage renal disease, but requires careful monitoring. 2, 4

• Monitor renal function closely when initiating or escalating doses, especially in patients reporting severe gastrointestinal reactions that could lead to dehydration 4, 1
• Acute kidney injury and worsening chronic renal failure have been reported, particularly from dehydration secondary to severe gastrointestinal effects 4, 5
• No dose adjustment is required for renal impairment, but vigilant monitoring for gastrointestinal side effects and adequate hydration is essential 4, 5

Diabetic Retinopathy

Patients with a history of diabetic retinopathy should be monitored closely, as semaglutide has been associated with diabetic retinopathy complications in clinical trials. 1

• The risk appears related to rapid and marked glucose and A1C reductions 2
• This is particularly important in patients also treated with insulin 5
• The American College of Cardiology specifically highlights this as a caution requiring close monitoring 2, 4

Gastroparesis

Semaglutide is not recommended in patients with clinically meaningful gastroparesis. 2, 4

• Semaglutide delays gastric emptying, which may worsen symptoms in patients with pre-existing gastroparesis 2
• This effect may slow absorption of concomitantly administered oral medications 2, 1
• Patients with prior gastric surgery (including bariatric surgery) require careful consideration 2, 4

Clinical Situations Requiring Dose Adjustment or Enhanced Monitoring

Hypoglycemia Risk with Concomitant Medications

When Ozempic is used with insulin secretagogues (e.g., sulfonylureas) or insulin, lower the dose of these medications to reduce hypoglycemia risk. 2, 1

• Semaglutide itself carries very low intrinsic hypoglycemia risk due to glucose-dependent insulin secretion 4
• The increased hypoglycemia risk occurs only when combined with insulin or insulin secretagogues 2, 4

Gallbladder Disease

Monitor for cholelithiasis (gallstones) and cholecystitis, as semaglutide increases the risk of gallbladder-related complications. 2, 4

• The mechanism is related to rapid weight loss and altered bile composition 4
• This requires ongoing clinical surveillance during treatment 4, 5

Oral Contraceptive Interactions

For patients using oral hormonal contraceptives, switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and after each dose escalation. 2, 4

• This is due to delayed gastric emptying potentially affecting absorption of oral contraceptives 2, 4
• The effect on absorption is usually transient but warrants precautionary measures 2

Common Pitfalls to Avoid

• Never share an Ozempic pen between patients, even if the needle is changed 1
• Do not ignore severe gastrointestinal symptoms: These can lead to dehydration and acute kidney injury, particularly in patients with pre-existing renal disease 4, 1
• Monitor medications with narrow therapeutic index (e.g., warfarin) as delayed gastric emptying may affect their absorption 4
• Ensure proper administration timing: Patients must understand dosing instructions to maximize efficacy and minimize side effects 6