What are the key considerations and questions to ask when managing a patient with a history of pancreatitis, thyroid cancer, or kidney disease, who is taking tirzepatide (a dual GIP and GLP-1 receptor agonist) for diabetes management?

Key Questions to Ask When Managing a Patient on Tirzepatide

Absolute Contraindications and Safety Screening

Before initiating or continuing tirzepatide, you must screen for absolute contraindications that preclude its use.

• Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) – This is an absolute contraindication based on animal studies showing thyroid C-cell tumors 1.
• History of severe hypersensitivity reactions to tirzepatide or its excipients, including anaphylaxis or angioedema 1.
• Current pregnancy status – Tirzepatide may cause fetal harm based on animal studies; women of reproductive potential should be counseled 1.

Pancreatitis History and Monitoring

Ask specifically about any history of pancreatitis, as tirzepatide has not been studied in patients with prior pancreatitis.

• Have you ever had pancreatitis? If yes, use with extreme caution and monitor closely for signs of recurrence 1, 2.
• Are you experiencing persistent severe abdominal pain? This could indicate acute pancreatitis, which occurs rarely (≤1%) but requires immediate discontinuation 2, 1.
• Pancreatitis has been reported in clinical trials, though causality has not been definitively established 3.

Kidney Disease Assessment

Tirzepatide requires careful monitoring in patients with kidney disease, though no dose adjustment is needed.

• What is your current kidney function (eGFR)? No dose adjustment is required even with eGFR <30 mL/min/1.73 m² or end-stage renal disease 1.
• Are you experiencing severe gastrointestinal symptoms? Monitor renal function when initiating or escalating doses in patients with renal impairment who report severe GI reactions, as dehydration can precipitate acute kidney injury 1.
• Tirzepatide reduces albuminuria and slows eGFR decline, providing kidney-protective benefits 4, 3.

Gallbladder Disease Risk

Screen for symptoms of gallbladder disease, as tirzepatide increases risk of cholelithiasis and cholecystitis.

• Do you have any history of gallstones or gallbladder problems? 1, 2.
• Are you experiencing right upper quadrant abdominal pain, especially after eating? This could indicate acute gallbladder disease, which occurs rarely but requires gallbladder studies and clinical follow-up 1, 2.
• Rates of cholelithiasis and cholecystitis are extremely low (≤1%) but warrant vigilance 2.

Concomitant Medications and Hypoglycemia Risk

Identify all glucose-lowering medications to prevent severe hypoglycemia.

• Are you taking insulin or sulfonylureas? These dramatically increase hypoglycemia risk when combined with tirzepatide 1, 3.
  • Reduce basal insulin by 20% immediately when starting tirzepatide 3.
  • Consider discontinuing or reducing sulfonylurea doses by 50% to prevent hypoglycemia 3.
• Are you taking DPP-4 inhibitors? These should be discontinued before starting tirzepatide, as concurrent use provides no additional benefit 3.

Gastrointestinal Tolerance and Nutritional Status

Assess baseline GI function and monitor for severe adverse reactions.

• Do you have severe gastroparesis or other severe gastrointestinal disease? Tirzepatide has not been studied in these patients and is not recommended 1.
• Are you experiencing nausea, vomiting, or diarrhea? GI adverse events occur in 39-49% of patients in a dose-dependent manner, with nausea and diarrhea being most common 2, 5.
• Have you been unable to eat or drink adequately? Severe GI reactions can lead to dehydration and acute kidney injury 1.
• In rare cases, hypoglycemic ketoacidosis has occurred in non-diabetic patients with severe GI symptoms and inadequate oral intake 6.

Diabetic Retinopathy Monitoring

For patients with diabetes and existing retinopathy, close monitoring is essential.

• Do you have a history of diabetic retinopathy? Tirzepatide has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema 1.
• Monitor these patients closely for progression of retinopathy 1.

Contraception and Reproductive Planning

For women of reproductive potential, address contraceptive efficacy.

• Are you using oral contraceptives? Tirzepatide delays gastric emptying (largest after the first dose) and may reduce efficacy of oral hormonal contraceptives 1.
• Switch to a non-oral contraceptive method or add barrier contraception for 4 weeks after initiation and for 4 weeks after each dose escalation 1.

Perioperative Planning

Identify any planned surgeries or procedures requiring anesthesia.

• Do you have any upcoming surgeries or procedures? Tirzepatide delays gastric emptying, creating aspiration risk during general anesthesia or deep sedation 1.
• Discontinue tirzepatide at least 3 weeks before elective surgery (three half-lives) to minimize delayed gastric emptying and aspiration risk 1.
• Retained gastric contents have been documented even after extended fasting periods in 24.2% of patients on GLP-1 receptor agonists 7.

Cardiovascular Disease Status

Assess cardiovascular risk to optimize treatment selection.

• Do you have established cardiovascular disease (prior MI, stroke, peripheral arterial disease, or revascularization)? While tirzepatide shows favorable cardiovascular safety trends, semaglutide has proven cardiovascular benefit with 20% reduction in cardiovascular death, nonfatal MI, or stroke 3.
• Tirzepatide meets cardiovascular safety criteria with MACE-4 hazard ratios <1.0 and upper confidence bounds <1.3 3.

Treatment Response and Adherence

Establish baseline metrics and monitoring plan.

• What is your current HbA1c and weight? Tirzepatide reduces HbA1c by 1.87-2.59% and achieves 20.9% weight loss at 72 weeks with the 15mg dose 5, 3.
• Can you commit to weekly subcutaneous injections? Adherence is critical for achieving therapeutic benefit 3.
• Assess treatment response at 12-16 weeks – if weight loss is <5% after 3 months at therapeutic dose, consider discontinuation and alternative approaches 3.

Common Pitfall to Avoid

Do not delay asking about thyroid cancer history or MEN2 syndrome – this is an absolute contraindication that must be identified before the first dose 1. Missing this screening question could expose patients to unnecessary risk given the black box warning for thyroid C-cell tumors in animal studies 1.