What are the contraindications for GLP-1 (Glucagon-Like Peptide-1) injections like Ozempic (semaglutide) or Tirzepatide?

Contraindications for GLP-1 Receptor Agonists (Ozempic/Semaglutide and Tirzepatide)

GLP-1 receptor agonists like Ozempic (semaglutide) and tirzepatide have only two absolute contraindications: personal or family history of medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia syndrome type 2 (MEN2), plus known hypersensitivity to the medication. 1

Absolute Contraindications

The FDA-approved labeling for semaglutide explicitly lists the following absolute contraindications 1:

• Personal or family history of medullary thyroid carcinoma (MTC) - This is based on animal studies showing thyroid C-cell tumors, though this has not been demonstrated in humans 2
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 2, 3
• Known hypersensitivity to semaglutide or any product components 1

These same contraindications apply to tirzepatide and other GLP-1 receptor agonists 4, 5.

Relative Contraindications and Cautions

Renal Impairment

• Severe renal impairment or end-stage renal disease (ESRD) is a contraindication for exenatide and lixisenatide specifically 2
• Liraglutide and semaglutide should be used with caution in severe renal impairment or ESRD, though they can be initiated with eGFR as low as 20-29 mL/min/1.73 m² 2
• Monitor for acute kidney injury, particularly in patients experiencing severe gastrointestinal symptoms (nausea, vomiting, diarrhea) that can cause dehydration 1

Pancreatitis

• Use with caution in patients with history of pancreatitis 2
• Not recommended in patients with suspected or confirmed acute pancreatitis 4
• Discontinue immediately if pancreatitis is suspected and do not restart if confirmed 1

Diabetic Retinopathy

• Semaglutide specifically has been associated with diabetic retinopathy complications, particularly in patients with pre-existing proliferative retinopathy 2, 1
• The absolute risk increase is larger among patients with baseline diabetic retinopathy (8.2% vs 5.2% placebo) compared to those without (0.7% vs 0.4% placebo) 1
• Patients with diabetic retinopathy history should be monitored for progression 2

Gastroparesis and Gastric Surgery

• Avoid in clinically meaningful gastroparesis 2
• Use caution in patients with prior gastric surgery due to delayed gastric emptying effects 2
• Shorter-acting agents may slow absorption of concomitant oral medications 2

Pregnancy and Breastfeeding

• Contraindicated in pregnancy and breastfeeding 2, 5

Important Drug Interactions and Monitoring

Hypoglycemia Risk

• Increased hypoglycemia risk when combined with insulin or insulin secretagogues (sulfonylureas) - dose reduction of these agents may be required 2, 1
• GLP-1 receptor agonists do not cause hypoglycemia when used alone or with metformin 2, 6

Gallbladder Disease

• Use caution in patients with history of cholelithiasis 2
• Monitor for acute gallbladder disease 2, 1

Common Adverse Effects (Not Contraindications)

The most common side effects include 2, 6:

• Nausea (15-44% of patients)
• Vomiting
• Diarrhea (13-18%)
• Constipation (10-30%)

These gastrointestinal symptoms typically occur early in treatment and diminish over time with gradual dose titration 2.

Key Clinical Pitfall

Do not confuse Hashimoto's thyroiditis with medullary thyroid carcinoma - GLP-1 receptor agonists can be safely used in patients with Hashimoto's thyroiditis, as the only thyroid-related contraindication is MTC or MEN2 3. This is a common source of confusion in clinical practice.