What are the contraindications to Moujaro (tirzepatide) in patients with type 2 diabetes, particularly those with a history of medullary thyroid carcinoma, pancreatitis, or impaired renal function?

Contraindications to Moujaro (Tirzepatide)

Absolute Contraindications

Moujaro 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). 1, 2, 3

• This contraindication is based on rodent studies showing thyroid C-cell tumors, though human relevance has not been definitively established 1, 2
• The contraindication applies even if the patient has not undergone genetic testing for MEN 2 4
• This is a class effect for all GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists 4, 3

History of Pancreatitis

Do not initiate Moujaro in patients at high risk for pancreatitis, and permanently discontinue if pancreatitis is confirmed. 1, 5

• If acute pancreatitis is definitively diagnosed while on tirzepatide, there is an absolute contraindication to restart any GLP-1 or dual GIP/GLP-1 medication 5
• Acute pancreatitis has been reported with GLP-1 receptor agonists, though causality has not been definitively established 1, 6
• If pancreatitis was only suspected but never confirmed, use extreme caution and consider alternative agents 5

Pregnancy and Breastfeeding

Moujaro is contraindicated in pregnancy and breastfeeding. 1, 2

• Women of reproductive potential must use reliable contraception 1
• For patients using oral hormonal contraceptives, consider switching to non-oral methods or adding barrier methods for 4 weeks after initiation and each dose escalation due to delayed gastric emptying affecting absorption 1, 2

Relative Contraindications and Precautions

Gastroparesis

Moujaro is not recommended in patients with clinically meaningful gastroparesis. 1, 2

• Tirzepatide delays gastric emptying and will worsen gastroparesis symptoms 1, 2
• Patients with prior gastric surgery, including bariatric procedures, require extreme caution 2

Gallbladder Disease

Avoid use in patients at high risk for gallbladder disease. 1

• Evaluate for gallbladder disease if cholelithiasis or cholecystitis is suspected 1
• There is an increased risk of gallstones and cholecystitis, particularly with rapid weight loss 1, 2

Diabetic Retinopathy

Close monitoring is required in patients at high risk for diabetic retinopathy. 1

• This particularly applies to older individuals and those with longer duration of type 2 diabetes (≥10 years) 1
• Monitor closely for progression of diabetic retinopathy 2

Renal Impairment Considerations

No dose adjustment is required for renal impairment, including end-stage renal disease. 1, 7, 8

• Tirzepatide exposure is similar across all levels of renal function 7
• Monitor renal function closely when initiating or escalating doses, especially in patients experiencing severe gastrointestinal side effects that could lead to dehydration 2, 8
• Tirzepatide has demonstrated positive effects on albuminuria without detrimental effects on eGFR 8, 9

Critical Dosing Considerations

Always start at the lowest dose (2.5 mg weekly) and titrate slowly to minimize gastrointestinal side effects. 1, 2

• Starting at high doses bypasses the body's adaptation period to delayed gastric emptying, dramatically increasing risk of severe nausea, vomiting, and dehydration 2
• Impact on drug absorption may occur during dose titration, particularly affecting medications with narrow therapeutic indices 1, 2

Hypoglycemia Risk

When combined with insulin or sulfonylureas, reduce doses of these medications to prevent hypoglycemia. 1, 2

• Tirzepatide itself has minimal intrinsic hypoglycemia risk due to glucose-dependent insulin secretion 1
• Increased hypoglycemia risk occurs only when combined with insulin secretagogues 1, 2