Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used in the treatment of obesity and diabetes mellitus because of their efficacy in weight reduction, glycemic control, and overall metabolic benefits. Gastrointestinal adverse events are among the most frequently reported side effects associated with these agents and are typically transient, occurring predominantly during dose escalation. However, severe gastrointestinal intolerance requiring hospitalization has rarely been reported. We present the case of a 51-year-old woman with obesity, hypertension, hyperlipidemia, and anxiety who developed severe nausea, vomiting, and diarrhea one day after restarting semaglutide 2.4 mg following a five-week treatment interruption during Ramadan. The patient had previously tolerated semaglutide therapy for approximately one year, with successful weight loss. Laboratory evaluation revealed significant electrolyte abnormalities, while contrast-enhanced abdominal and pelvic CT showed no acute pathology. The patient was managed with supportive treatment, including intravenous hydration, electrolyte replacement, antiemetics, and dietary modifications. She was discharged after four days of hospitalization, and cautious semaglutide reinitiation with dose escalation was planned after two weeks. This case highlights an important educational opportunity during Ramadan counseling, as patients receiving GLP-1 receptor agonists should generally be advised not to discontinue therapy solely because of daytime fasting unless clinically indicated. If treatment interruption occurs for a prolonged period, cautious reinitiation beginning at a lower dose with gradual dose escalation should be considered to minimize gastrointestinal adverse events. Careful dose re-titration after extended lapses in therapy may help reduce this risk. Further studies are needed to establish evidence-based recommendations for semaglutide reinitiation after prolonged treatment interruptions.
