Cases of acute cholecystitis linked to GLP-1 receptor agonist use in US
Researchers have found 36 cases of acute cholecystitis associated with the use of GLP-1 receptor agonists in the U.S., according to findings from the FDA Adverse Event Reporting System published in JAMA Internal Medicine.
“The required labeling for some GLP-1 receptor agonists indicated for glycemic control in patients with type 2 diabetes include warnings and precautions regarding acute gallbladder disease in the U.S. Prescribing Information ... while others do not,” Daniel Woronow, MD, medical officer in the Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of Pharmacovigilance at the FDA, and colleagues wrote. “The FDA recently reviewed the Adverse Event Reporting System to identify cases of acute cholecystitis associated with the GLP-1 receptor agonist products that did not have warnings and precautions regarding acute gallbladder disease.”
Researchers reviewed the FDA Adverse Event Reporting System from the date of the first approved GLP-1 receptor agonist on April 28, 2005, through Sept. 16, 2021, for cases of acute cholecystitis associated with GLP-1 use. Acute cholecystitis cases were identified through compatible signs and symptoms treated with cholecystectomy, a confirmatory pathology report, or a diagnosis from a health care provider. Demographics, reason for GLP-1 use, time to acute cholecystitis onset, dosage and patient outcomes were collected.
There were 36 cases of acute cholecystitis found, with 21 coming from adults using exenatide (Bydureon/Byetta, AstraZeneca), seven from those using dulaglutide (Trulicity, Eli Lilly), seven from semaglutide (Ozempic, Novo Nordisk) users and one associated with lixisenatide (Adlyxin, Sanofi). A cholecystectomy was performed in 30 cases, two cases were resolved with ursodeoxycholic acid treatment and GLP-1 discontinuation, one person had an unrelated cerebrovascular accident, and one person died within 24 hours of cholecystitis presentation. Serious outcomes were reported in all cases. Seven adults developed pancreatitis, with two deaths, and one person had fatal liver necrosis.
The time from GLP-1 receptor agonist initiation to onset of acute cholecystitis was less than 90 days in 47% of cases. Acute cholecystitis occurred in 14 people taking the recommended starting GLP-1 dose and in 14 taking the maximum recommended dose. Time to acute cholecystitis onset was shorter for those taking the recommended starting dose vs. the maximum starting dose (49 days vs. 16 months) since most adults on the higher dose were titrated up from the recommended starting dose.
“This case series provides patient-level data that complement the findings of a meta-analysis by He et al of the association of cholecystitis with GLP-1 receptor agonists,” the researchers wrote. “Potential mechanisms include weight loss, suppression of cholecystokinin secretion and reduced gallbladder emptying.”
Reference:
- He L, et al. JAMA Intern Med. 2022;doi:10.1001/jamainternmed.2022.0338.
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