Contraindications for Tirzepatide
Tirzepatide 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), and in those with a history of serious hypersensitivity reactions to tirzepatide. 1, 2
Absolute Contraindications
Thyroid C-Cell Tumor Risk
- Personal or family history of medullary thyroid carcinoma is an absolute contraindication 1, 2
- Multiple endocrine neoplasia syndrome type 2 (MEN 2) is an absolute contraindication 1, 2
- This black box warning stems from evidence that GLP-1 receptor agonists can increase the risk of thyroid C-cell tumors 1, 3
Hypersensitivity
- History of serious hypersensitivity reaction to tirzepatide is an absolute contraindication 2
Dialysis Patients
- Patients on dialysis should not receive tirzepatide, as SGLT2 inhibitors (and by extension, similar glucose-lowering agents) are contraindicated in this population 1
Situations Requiring Extreme Caution (Use with Great Care or Avoid)
Gastrointestinal Conditions
- Gastroparesis - avoid use due to delayed gastric emptying effects 2, 3
- Prior gastric surgery - use with caution due to altered gastric anatomy and emptying 2
- Clinically meaningful gastroparesis - use with extreme caution 2
Pancreatic Disease
- History of acute pancreatitis - use with caution and monitor closely 1, 2
- While acute pancreatitis rates are extremely low (≤1%), the history of pancreatitis warrants careful consideration 4
Renal Impairment
- Severe renal impairment or end-stage renal disease - use with caution 2
- Unlike exenatide (which is contraindicated with eGFR <30), tirzepatide does not have a strict eGFR cutoff, but renal function should be monitored, especially in patients with nausea and possible dehydration 1
- Monitor renal function closely when initiating or increasing doses in patients with kidney disease 2
Perioperative Considerations
- Patients requiring general anesthesia - careful timing of tirzepatide administration is necessary due to delayed gastric emptying and increased risk of pulmonary aspiration 3
Clinical Pitfalls to Avoid
Hypoglycemia Risk
- When combining tirzepatide with insulin or insulin secretagogues (sulfonylureas), lower doses of these medications may be required to prevent hypoglycemia 2
- Monitor closely for hypoglycemia in these combinations 2
Drug Interactions
- Tirzepatide may affect absorption of oral medications with narrow therapeutic indices (such as warfarin) due to delayed gastric emptying 2
- Healthcare providers should monitor for consequences of delayed absorption 3
Diabetic Retinopathy
- While not a contraindication, monitor patients with history of diabetic retinopathy closely, as worsening has been reported with similar agents 2