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Absolute contraindications include: Personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) - this is included in a boxed warning Known serious hypersensitivity to tirzepatide or any excipients Regarding cardiovascular considerations, while there are no absolute cardiac contraindications, healthcare providers should exercise clinical judgment and careful monitoring in patients with: Heart failure , particularly if symptoms are not well-controlled Recent cardiovascular events , with individualized assessment of risks and benefits Cardiac arrhythmias , with monitoring of heart rate changes Significant dehydration risk , which could exacerbate cardiovascular conditions The FDA label does not specify renal function thresholds for contraindication, though monitoring renal function is advisable if severe gastrointestinal adverse reactions occur, as these may lead to dehydration and acute kidney injury

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This discovery also paved the path to additional GLP-1 agonists, like tirzepatide , a dual agonist that targets both GLP-1 and GIP receptors for even greater metabolic impact

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