PGY-2 Internal Medicine Resident UTRGV Edinburg, Texas, United States
Introduction: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia in the setting of resistance to peripheral action of insulin. The management of T2DM is challenging, and novel medications have shown promising results. One of these medications is Tirzepatide. Recently approved by the FDA, this medication works by activating both GLP-1 and GIP receptors, improving insulin secretion with convenient once-weekly dosing. Regarding its adverse reactions, the frequency of acute pancreatitis has not been defined. In this case, we present a patient with acute pancreatitis after increasing the dose of this medication.
Case Description: A 38-year-old Hispanic lady with pre-diabetes, anxiety, and major depressive disorder presented to the emergency department with worsening epigastric pain for the past ten days. The pain was initially presented as epigastric discomfort associated with watery diarrhea of 8-10 episodes per day, nausea, and vomiting. The abdominal pain was described as constant and sharp, 10/10 in intensity, radiating to the back bilaterally, and exacerbated by meals. She denied other symptoms or similar episodes. Medications included Escitalopram, Esomeprazole, Loperamide, Ketorolac, and Tirzeparatide, which was recently started two months ago. Tirzepatide had a dosage increase of up to 7.5 mg one day before starting her symptoms. Vital signs on admission were temperature of 97.9 F, HR 79 bpm, RR 15/min, BP of 104/63 mm Hg, and SpO2 of 100% on room air. Upon physical examination, there was tenderness on palpation of the epigastric region, with negative Murphy sign, rebound, or guarding. Admission labs revealed a Hematocrit of 39 %, BUN of 12 mg/dl (normal ref: 7-25), calcium of 9.8 mg/dl (normal ref: 8.6-10.3), AST of 17 IU/L (normal ref: 13-39), ALT of 17 IU/L (normal ref: 7-52), alkaline phosphatase 51 IU/L (normal ref: 34-104), bilirubin total 0.7 mg/dl (normal ref: 0.2-1.2), lipase level of 96 IU/L (normal ref: 11-82), and triglycerides level of 56 mg/dl (normal ref: 150). CT abdomen and pelvis with contrast revealed edematous changes in the pancreatic head and uncinate process region, with no parenchymal calcification, focal mass lesion, or collection. Abdominal ultrasound revealed small amount of gallbladder sludge but no cholelithiasis or cholecystitis. The patient was admitted for acute mild pancreatitis. The hospital course was uncomplicated, with an overall improvement in her symptoms. Tirzeparatide was discontinued upon discharge.
Discussion: It is well known that incretin-based therapies are associated with acute pancreatitis. Proposed mechanisms include the overgrowth of exocrine duct cells, resulting in hyperplasia, occlusion and back pressure leading to pancreatic inflammation. Our literature search did not find a case report of Tizepatide-induced pancreatitis. In this case, the medication was used in a pre-diabetic patient, which is currently not included as the standard of care. Our patient also had small amount of biliary sludge, which could be debated as the possible source of pancreatitis. Due to the recent release of this medication, a closer observation would be recommended.