What is the recommended screening process for patients being considered for Tirzepatide (Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist) therapy, particularly those with a history of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2, pancreatitis, or pancreatic cancer, and impaired renal (kidney) function or liver function?

Tirzepatide Pre-Treatment Screening Protocol

Before initiating tirzepatide, screen all patients for personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2), and avoid use if either is present; additionally, assess renal function with eGFR and screen for active pancreatitis or symptomatic gallbladder disease. 1, 2

Absolute Contraindications Requiring Screening

Thyroid Cancer Risk Assessment

• Obtain detailed personal and family history of medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia syndrome type 2 (MEN 2). 1
• Do not prescribe tirzepatide if the patient has any personal history of MTC or any family history of MTC or MEN 2. 1
• This represents an absolute contraindication based on the mechanism of GLP-1 receptor agonism, which has been associated with thyroid C-cell tumors in animal studies. 1
• MEN 2B patients develop MTC at younger ages with 100% developing invasive carcinoma, making this screening particularly critical. 3

Pancreatitis History

• Screen for any history of pancreatitis (acute or chronic) before initiating tirzepatide. 2
• If pancreatitis is suspected or confirmed, discontinue tirzepatide immediately and do not restart. 2
• Patients with prior pancreatitis are at higher risk for recurrence with incretin-based therapies. 2

Gallbladder Disease Assessment

• Evaluate for symptomatic cholelithiasis or active cholecystitis before starting tirzepatide. 2
• For patients with asymptomatic gallstones, consider baseline gallbladder ultrasound to document stone burden and counsel patients about warning signs (right upper quadrant pain, nausea, vomiting, fever). 2
• For patients with symptomatic cholelithiasis, strongly consider cholecystectomy before initiating tirzepatide, as rapid weight loss compounds baseline gallstone risk. 2
• Avoid tirzepatide in patients with acute cholecystitis or recent biliary colic until the acute condition is resolved. 2

Renal Function Screening

Kidney Function Assessment

• Measure eGFR and urine albumin-to-creatinine ratio (ACR) before starting tirzepatide. 1
• Tirzepatide can be used in patients with eGFR ≥20 mL/min/1.73 m², though dose adjustments are not specifically required based on renal function alone. 1
• For patients with type 2 diabetes and CKD (eGFR ≥20 mL/min/1.73 m²), a GLP-1 receptor agonist with proven cardiovascular benefit is recommended when metformin and/or SGLT2 inhibitors are insufficient or cannot be used. 1
• Metformin should be reduced to 1000 mg daily if eGFR is 30-44 mL/min/1.73 m² when used concomitantly. 1

Diabetic Kidney Disease Monitoring

• Screen all patients with type 2 diabetes annually for CKD starting at diagnosis using spot urine ACR and eGFR. 1
• Persistent abnormalities (ACR ≥30 mg/g or eGFR <60 mL/min/1.73 m² for ≥3 months) define CKD and should trigger evidence-based treatments. 1

Hepatic Function Screening

Liver Assessment

• Check baseline liver enzymes (ALT, AST) and consider GGT before initiating tirzepatide, particularly in patients taking other potentially hepatotoxic medications. 4
• Enhanced monitoring of liver function is warranted during treatment, especially in the first 6 months when adverse drug reactions most commonly occur. 4
• Acute liver injury has been reported with tirzepatide and was not mentioned in initial drug labeling. 4

Cardiovascular and Metabolic Screening

Baseline Metabolic Parameters

• Measure HbA1c, fasting glucose, lipid panel, and blood pressure before starting tirzepatide. 1, 5
• For patients with cardiovascular disease or those requiring weight-based medication dosing, intensify therapeutic drug monitoring. 4
• Tirzepatide has demonstrated cardiovascular benefits and improved surrogate markers of cardiovascular disease. 1

Weight and BMI Documentation

• Document baseline weight and BMI to track treatment response. 6
• Tirzepatide is indicated for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity. 6

Gastrointestinal Risk Assessment

Gastric Emptying Considerations

• Assess for conditions that may be affected by delayed gastric emptying, including gastroparesis or severe gastrointestinal disease. 1
• For patients scheduled for elective surgery, tirzepatide should be held appropriately (day before for daily dosing context, though tirzepatide is weekly) to minimize aspiration risk. 1
• The effect of tachyphylaxis on gastric emptying with long-term use remains unclear. 1

Medication Reconciliation

Drug Interaction Screening

• Review all concomitant medications, particularly oral contraceptives, as tirzepatide may impair oral drug absorption during dose titration. 2
• Identify patients taking hepatotoxic or nephrotoxic medications who require enhanced monitoring. 4
• For patients on insulin or sulfonylureas, plan for dose reduction to minimize hypoglycemia risk. 7, 5

Pancreatic Cancer Family History

While the provided evidence focuses on familial pancreatic cancer screening protocols 1, these guidelines address screening for pancreatic cancer itself rather than contraindications to tirzepatide use. There is no established contraindication to tirzepatide based solely on family history of pancreatic cancer, though active pancreatic disease or pancreatitis remains a contraindication. 2

Common Pitfalls to Avoid

• Do not overlook family history of MTC or MEN 2 during initial screening—this is an absolute contraindication that cannot be overridden. 1
• Do not start tirzepatide during active pancreatitis or acute cholecystitis—wait until resolution. 2
• Do not assume asymptomatic gallstones are safe—counsel patients and consider baseline imaging. 2
• Do not neglect baseline renal function assessment—this guides overall diabetes management strategy. 1
• Do not forget that most adverse drug reactions occur within the first 6 months, requiring closer monitoring during this period. 4