What are the contraindications for Ozempic (semaglutide)?

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 well as in those with known hypersensitivity to semaglutide or any product components. 1

Thyroid-Related Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC) is an absolute contraindication due to the FDA Black Box Warning regarding thyroid C-cell tumor risk based on rodent studies 2, 3, 1
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) is an absolute contraindication 2, 3, 1
• Important distinction: Primary hypothyroidism, hyperthyroidism, and autoimmune thyroid diseases (Hashimoto's thyroiditis, treated Graves' disease) are NOT contraindications—only MTC and MEN 2 are contraindicated 3

Hypersensitivity

• Known hypersensitivity to semaglutide or any product components is an absolute contraindication 1
• Severe allergic reactions and dermal hypersensitivity reactions have been documented 2, 4

Pregnancy and Breastfeeding

• Pregnancy is an absolute contraindication 2, 5
• Breastfeeding is an absolute contraindication, as safety has not been established 2

Relative Contraindications and High-Risk Situations Requiring Extreme Caution

Gastrointestinal Conditions

• Clinically meaningful gastroparesis: Semaglutide is not recommended in these patients as it delays gastric emptying and will worsen symptoms 2
• History of pancreatitis: Use with caution, as semaglutide has not been studied in these patients and acute pancreatitis risk is increased 2, 6, 7
• Prior gastric surgery (including bariatric surgery): Requires extreme caution due to altered gastric anatomy and delayed emptying effects 2

Renal Impairment

• Severe renal impairment (eGFR <30 mL/min/1.73 m²) requires careful monitoring due to increased risk of acute kidney injury from dehydration secondary to gastrointestinal side effects 2
• Unlike exenatide (which is contraindicated if eGFR <30), semaglutide can be used with caution but warrants close monitoring 2

Ophthalmologic Concerns

• History of diabetic retinopathy: Monitor closely for progression, as there is increased risk of diabetic retinopathy complications, particularly when combined with insulin 2, 7
• Untreated closed-angle glaucoma: Use with caution 2

Gallbladder Disease

• Increased risk of cholelithiasis (gallstones) and cholecystitis requires monitoring, particularly in patients with pre-existing gallbladder disease 2, 7

Critical Drug Interactions and Concomitant Medication Concerns

Hypoglycemia Risk

• When used with insulin, sulfonylureas, or glinides (insulin secretagogues), there is increased hypoglycemia risk requiring dose reduction of these medications 2, 6

Oral Contraceptive Efficacy

• For patients using oral hormonal contraceptives, switch to non-oral contraceptive method or add barrier method for 4 weeks after initiation and after each dose escalation due to delayed gastric emptying affecting absorption 2

Medications with Narrow Therapeutic Index

• Semaglutide delays absorption of concomitantly administered oral medications (particularly warfarin) due to delayed gastric emptying 2

Common Pitfalls to Avoid

• Never start at high doses: Always begin at 0.25 mg weekly for 4 weeks, then escalate to 0.5 mg, increasing only after at least 4 weeks at each dose level to minimize gastrointestinal side effects 2
• Screen for MTC/MEN 2 before prescribing: Despite being an absolute contraindication, studies show only 1.8% of patients had proper disease history assessment prior to initiation 8
• Monitor renal function closely: Especially when initiating or escalating doses in patients with pre-existing kidney disease or those experiencing severe gastrointestinal symptoms that could lead to dehydration 2
• Do not confuse thyroid conditions: Only MTC and MEN 2 are contraindications—common thyroid disorders like hypothyroidism are not 3