TIRZEPATIDE: CONTRAINDICATIONS AND FACTORS DETERMINING SIDE EFFECTS

Abstract

Tirzepatide is an innovative drug with a dual mechanism of action, acting as an agonist of GLP-1 (glucagon-like peptide 1) and GIP (gastrin-inhibiting peptide) receptors, indicated for glycemic control in patients with type 2 diabetes and weight reduction in obese or overweight individuals associated with comorbidities such as hypertension or dyslipidemia. The mechanism of action promotes glucose-dependent insulin secretion, reduces glucagon secretion, reduces appetite, and delays gastric evacuation, ensuring efficacy in both metabolic control and weight loss. It is essential to detail the contraindications to its use, classified as absolute and relative. Absolute contraindications include severe allergy to the drug or its excipients, pseudo-obstructive bowel syndrome, history of pancreatic neoplasia, and pregnancy/breastfeeding, situations in which the associated risk completely outweighs the therapeutic benefit. Relative contraindications include untreated chronic pancreatic disease, chronic gastrointestinal diseases (such as peptic ulcer or Crohn's disease), severe renal insufficiency (GFR <30 mL/min/1.73 m²), symptomatic bradycardia, and use in children under 18 years of age, requiring individual benefit-risk assessment and rigorous monitoring. Furthermore, factors determining the occurrence of side effects include gastrointestinal issues (nausea, vomiting, diarrhea), headache, and injection site reactions. Patient profile directly influences risk: elderly individuals over 75 years of age, individuals with comorbidities such as gastrointestinal neuropathy or malnutrition, and those with a BMI >40 kg/m² are more susceptible. Drug interactions are also relevant, especially with drugs dependent on gastric motility for absorption, hypoglycemic agents, and anticoagulants, which can increase the risk of hypoglycemia or alterations in plasma concentration. Therapeutic particularities, such as initial dose without gradual titration and prolonged duration of use, increase the frequency of complications. The objective of this study is to present clinical guidelines for the safe and effective prescription of tirrizepatide, minimizing risks to the patient through pre-treatment screening, continuous monitoring, and appropriate therapeutic adjustments.