GLP-1 analogues may be associated with bile duct, gallbladder disease
Current use of DPP-4 inhibitors was not associated with increased risk for bile duct and gallbladder disease versus current use of at least 2 oral antidiabetic drugs, but an increased risk was seen with use of GLP-1 analogues.
Glucagon-like peptide 1 (GLP-1) analogues were associated with increased risk for bile duct and gallbladder disease in a recent population-based cohort study in the United Kingdom.
Researchers linked data from the U.K. Clinical Practice Research Datalink and the Hospital Episodes Statistics database to determine whether current use of dipeptidyl-peptidase-4 (DPP-4) inhibitors and GLP-1 analogues, alone or as combination therapy, was linked with incident bile duct or gallbladder events causing hospitalization. Hazard ratios were estimated for DPP-4 inhibitor and GLP-1 analogue use versus use of at least 2 oral antidiabetic drugs. Results were published online Aug. 1 by JAMA Internal Medicine.
The study cohort included 71,369 patients at least 18 years of age who began taking an antidiabetic drug between Jan. 1, 2007, and March 31, 2014. Of these, 853 were hospitalized for bile duct and gallbladder disease over 227,994 person-years of follow-up (mean follow-up, 3.2 years; incidence rate per 1,000 person-years, 3.7; 95% CI, 3.5 to 4.0). Five hundred sixty-three patients had a diagnosis of cholelithiasis, 368 had a diagnosis of cholecystitis, 5 had a diagnosis of cholangitis, and 151 had a diagnosis of other bile duct and gallbladder disease; diagnosis categories were not mutually exclusive. Seventy-five patients (8.8%) underwent cholecystectomy.
Patients who used GLP-1 analogues were younger, were more likely to be obese, and were more likely to have previously used sulfonylureas and insulin versus patients using other antidiabetic drugs, the researchers noted. Current use of DPP-4 inhibitors was not associated with increased risk for bile duct and gallbladder disease versus current use of at least 2 oral antidiabetic drugs (adjusted hazard ratio, 0.99; 95% CI, 0.75 to 1.32), but an increased risk was seen with use of GLP-1 analogues (adjusted hazard ratio, 1.79; 95% CI, 1.21 to 2.67), the study found. A secondary analysis also found an increased risk of cholecystectomy associated with use of GLP-1 analogues (adjusted hazard ratio, 2.08; 95% CI, 1.08 to 4.02).
The authors noted that diabetes severity is an independent risk factor for bile duct or gallbladder disease and that confounding by indication could be possible. They also mentioned the potential for underestimation of drug exposure and overdetection or misdiagnosis of bile duct and gallbladder disease in patients who were taking GLP-1 analogues. However, they concluded that their results point to an association between bile duct and gallbladder disease and use of GLP-1 analogues. Although further studies are needed, they wrote, “physicians prescribing GLP-1 analogues should be aware of this association and carefully monitor patients for biliary tract complications.”