Use of some diabetes drugs linked to risk of acute gallbladder disease, FDA reports
Patients who take glucagon-like peptide-1 receptor agonists for weight loss or management of diabetes may be at risk of acute gallbladder disease.
USA: In a recent study published as a research letter in JAMA Internal Medicine, the FDA presented the results of its reviewal of the FDA Adverse Event Reporting System (FAERS). The review was done to identify cases of acute cholecystitis (AC) tied to the intake of glucagon-like peptide-1 (GLP-1) agonists that did not have warnings and precautions on acute gallbladder disease.
The study found 36 cases of acute cholecystitis among patients taking GLP-1 receptor agonists for weight loss or diabetes medications, 42% of whom experienced the disease onset within three months of starting treatment, and three of the patients died.
The researchers from FDA identified postmarketing cases of acute cholecystitis from 2005 to 2016 in 21 patients taking exenatide (Byetta), seven on semaglutide (Ozempic), seven taking dulaglutide (Trulicity), and one patient taking lixisenatide (Adlyxin).
Other findings of the study are as follows:
- Thirty of the cases were treated with cholecystectomy and two resolved with ursodeoxycholic acid treatment and discontinuation of the GLP-1 receptor agonist.
- Of the three patients who died, two had pancreatitis and one died from fatal liver necrosis.
- In 42% of the cases, patients experienced disease onset within 90 days from the time of treatment initiation.
According to Daniel Woronow, and colleagues from the US Food and Drug Administration, the case series are in accordance with the results of a recent meta-analysis of 76 randomized trials that detected an association between cholecystitis and GLP-1 receptor agonists. The potential mechanisms include suppression of cholecystokinin secretion, weight loss, and reduced gallbladder emptying, they explained.
Based on pathology reports, diagnosis by a healthcare provider, or compatible signs and symptoms treated with cholecystectomy, a total of 36 cases of acute cholecystitis were identified. Patients with cholelithiasis or cholecystitis prior to the use of a GLP-1 receptor agonist or cases where an alternative cause of cholecystitis was suspected were excluded.
Nine patients were shown to have weight loss before diagnosis (mean 7.6 kg). 2 patients were also receiving fenofibrate, which comes with a labeled warning of cholelithiasis.
The study findings are significant as some GLP-1 RAs indicated for blood sugar control in type 2 diabetes patients require labeling including precautions and warnings regarding cute gallbladder disease in the US Prescribing Information (the prescribing information approved by the US Food and Drug Administration [FDA]), while other do not.
Reference:
Woronow D, Chamberlain C, Niak A, Avigan M, Houstoun M, Kortepeter C. Acute Cholecystitis Associated With the Use of Glucagon-Like Peptide-1 Receptor Agonists Reported to the US Food and Drug Administration. JAMA Intern Med. Published online August 29, 2022. doi:10.1001/jamainternmed.2022.3810
