A Probable Case of Tirzepatide-Induced Acute Pancreatitis

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists have become increasingly popular for their dual benefits in glycaemic control and weight reduction. However, emerging concerns have been raised regarding their association with acute pancreatitis. Tirzepatide, a novel dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist, is currently a subject of concern. We report the case of a 32-year-old woman with a prior history of gestational diabetes mellitus, who presented with a three-week history of worsening epigastric pain, nausea, vomiting, and constipation. The patient had commenced tirzepatide (Mounjaro) five weeks earlier for weight loss, with five doses administered prior to admission. She had received 2.5 mg subcutaneously weekly for four weeks, followed by one dose of 5 mg subcutaneously. Examination revealed severe epigastric tenderness without peritonism. Laboratory tests showed markedly elevated lipase (11,645 U/L), transaminases, alkaline phosphatase, and bilirubin levels. Imaging findings were consistent with acute interstitial oedematous pancreatitis and revealed incidental gallstones without signs of choledocholithiasis or cholecystitis. CT and magnetic resonance cholangio-pancreatography (MRCP) confirmed pancreatic inflammation without biliary obstruction. The patient was managed conservatively with cessation of tirzepatide, supportive care, and close monitoring. She showed significant clinical improvement with normalisation of lipase levels by discharge. This case raises concerns over the potential risk of pancreatitis associated with tirzepatide use. Although the patient's pancreatitis may appear to be most consistent with gallstone-induced aetiology, the recent initiation of tirzepatide may be a potential contributing factor, as the strong temporal correlation between drug initiation and symptom onset, coupled with clinical resolution upon discontinuation, suggests a probable causal relationship. Clinicians should maintain a high index of suspicion for drug-induced pancreatitis in patients using GLP-1 receptor agonists, including tirzepatide, especially in those with pre-existing metabolic risk factors or gallstones. This case underscores the need for continued surveillance and more robust data to guide the safe use of tirzepatide in routine clinical practice.

Keywords: acute pancreatits; glp-1 receptor agonist; medication-induced pancreatitis; multiple gallstones; tirzepatide.

Figure 1. CT Abdomen and Pelvis with contrast

The distal head and tail are bulky with peripancreatic inflammatory changes and peripancreatic fluid. Imaging features are in keeping with mild acute interstitial oedematous pancreatitis and mild ascites.