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BOSTON — Clinicians at internal medicine and endocrinology meetings recently presented case reports describing pancreatitis in patients taking tirzepatide. In one case, a 64-year-old patient died.

Clinicians and patients should be aware of this complication, especially as more patients take this type of antidiabetic and weight loss medication, researchers said.

Krista Grennan, MD, a resident with Mayo Clinic in Jacksonville, Florida, and colleagues described the fatal complication in a poster presented at the American Association of Clinical Endocrinology meeting in May.

"While tirzepatide has known significant weight loss benefits, physicians should be aware of the rare but potentially fatal side effects before initiating treatment," they wrote. "A case-by-case risk benefit analysis should be performed for each patient."

The 64-year-old patient arrived at the emergency department with sudden epigastric pain. She had recently started tirzepatide for weight loss and had taken her last dose 4 days prior, according to Grennan and coauthors. A CT scan showed acute pancreatitis and possible necrosis.

The next day, another CT scan showed severe necrotizing pancreatitis and hypoperfusion of several organs. The patient developed acute hypoxic respiratory failure and required intubation.

The patient's condition worsened on day 3. Clinicians initiated a stroke protocol after the patient developed asymmetric pupils. The patient developed asystole before brain imaging could be performed and was pronounced deceased.

The medication label notes the risk for acute pancreatitis was observed in clinical trials and warns, "Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed."

Grennan and colleagues said that the alert should be further emphasized in a black box warning.

However, Sonal Singh, MD, MPH, associate professor at UMass Chan Medical School in Worcester, Massachusetts, said another cause of pancreatitis in the patient may have been the cause. Still, clinicians should inform patients about signs of the condition such as nausea, vomiting, abdominal pain, and fever, said Singh, who was not involved in the new case presentations but has studied the risk for pancreatitis with other glucagon-like peptide 1 (GLP-1)–based therapies.

"Consider holding these drugs when such symptoms and signs emerge," he said.

The label for tirzepatide notes that after starting treatment, clinicians should "observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting)."

A Low Threshold to Stop

At the Society of General Internal Medicine (SGIM) 2024 Annual Meeting in May, Mohammed Abdelsalam, MD, a resident at Texas Tech University Health Sciences Center in Amarillo, Texas, presented a case of necrotizing pancreatitis and cholecystitis in a 25-year-old woman taking tirzepatide for weight loss. In this case, the patient had a good prognosis, he said.

The patient had "intermittent episodes of severe epigastric pain radiating to the back and right upper quadrant abdominal pain along with nausea and vomiting for few days," Abdelsalam said. The patient was taking weekly injections of tirzepatide and had lost 30 lb in 6 months.

After physical examination, lab tests, and imaging that showed peripancreatic stranding and fluid, the patient received IV fluids and antibiotics, and a cholecystectomy was ordered.

"Healthcare providers should be aware that cholelithiasis, cholecystitis, and pancreatitis are rare adverse effects (0.2%) that can occur with GLP-1" receptor agonist agents, including tirzepatide, Abdelsalam told Medscape Medical News. "The incidence of these conditions is expected to rise with the increased prescriptions of these agents."

Higher doses, treatment for more than 26 weeks, and rapid weight loss may be risk factors. A history of pancreatitis, hypertriglyceridemia, cholelithiasis, and alcohol use also may heighten the risk, he said.

"There should be a low threshold for stopping tirzepatide if pancreatitis is suspected," Abdelsalam said.

Case reports can add to clinicians' understanding of adverse events but "need to be synthesized and seen in light of other reports and studies," Singh told Medscape Medical News.

For instance, at Digestive Disease Week, researchers presented a new analysis of data from a real-world healthcare database that found that the link between GLP-1 drugs and pancreatitis might be attenuated after accounting for patients' initial body mass index.

The study — which did not include tirzepatide as part of the analysis — was framed as a counterpoint to another study that found that GLP-1 agonists increased the risk for pancreatitis.

Singh said he sees the findings from both studies as consistent in showing an increased risk, with any differences in the results likely reflecting the different data sources, study designs, and populations.