TIRZEPATIDE AND INTESTINAL MOTILITY DISORDERS: PATHOPHYSIOLOGICAL FACTORS, FECALITH FORMATION, AND HYDRO-ELECTROLYTE IMBALANCES ASSOCIATED WITH DIARRHEA

Abstract

Introduction: Tirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide type 1 (GLP-1) receptors, used in the treatment of type 2 diabetes mellitus and, according to the approved indication, in the management of obesity. Despite its metabolic benefits, the medication is associated with gastrointestinal adverse effects, especially nausea, diarrhea, vomiting, and constipation. These manifestations can compromise the regularity of intestinal transit and, in specific situations, contribute to relevant clinical complications. Objective: To analyze the pathophysiological mechanisms involved in intestinal transit disorders associated with tirzepatide, with emphasis on constipation, the formation of fecaliths, the possibility of paradoxical diarrhea and fluid and electrolyte imbalances resulting from gastrointestinal losses. Methodology: Narrative review of the literature, based on regulatory information, clinical studies and scientific publications related to the pharmacology of tirzepatide, the gastrointestinal effects of GLP-1 receptor agonists and the pathophysiology of fecal impaction and diarrhea. Discussion: The incretin action of tirzepatide modifies gastrointestinal physiology, mainly by delaying gastric emptying and influencing neurohormonal mechanisms related to digestive motility. Although diarrhea and constipation are recognized adverse events, fecalith formation should not be considered an inevitable or directly proven consequence of the medication. However, severe constipation can favor the retention and hardening of feces, culminating in fecal impaction. In this circumstance, paradoxical diarrhea may occur, characterized by the passage of liquid content around the retained fecal mass. Persistent diarrhea and vomiting, in turn, can cause dehydration, changes in potassium and bicarbonate and impaired kidney function. Conclusion: Early recognition of changes in intestinal transit during treatment with tirzepatide is essential to prevent complications. Clinical assessment should consider both primary diarrhea related to the medication and the possibility of severe constipation with fecal impaction, especially in the face of abdominal pain, distension, reduced stool elimination or signs of dehydration.