Clinical trials have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may be associated with a higher risk of biliary-related diseases in patients with type 2 diabetes. Limited real-world studies have examined the comparative biliary safety of GLP-1RAs versus other antihyperglycemic drugs.
To estimate the comparative risk of biliary-related diseases between GLP-1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is), which are indicated for patients with similar diabetes severity in Taiwan.
We identified patients with type 2 diabetes initiating GLP-1RAs or SGLT2is from a nationwide Taiwanese database during 2012 to 2018. We used an on-treatment approach to examine the effect of continuous use and an intention-to-treat approach to assess the effect of initiation of GLP-1RAs versus SGLT2is. We used Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the composite hospitalized biliary-related diseases, including acute cholecystitis or cholecystectomy, choledocholithiasis, and acute cholangitis, after matching each GLP-1RA initiator to up to 10 SGLT2i initiators using propensity scores (PSs).
Among 78,253 PS-matched patients, GLP-1RA use was associated with a numerically higher risk of biliary-related diseases versus SGLT2i use in the on-treatment analysis, with an HR of 1.20 (95% CI, 0.93-1.56) for the composite outcome, an HR of 1.22 (95% CI, 0.92-1.62) for acute cholecystitis or cholecystectomy, an HR of 1.20 (95% CI, 0.69-2.07) for choledocholithiasis, and an HR of 1.14 (95% CI, 0.82-2.42) for acute cholangitis. The HRs were more pronounced in the intention-to-treat analysis (1.27 [95% CI, 1.05-1.53] for the composite outcome, 1.29 [95% CI, 1.04-1.58] for acute cholecystitis or cholecystectomy, 1.74 [95% CI, 1.23-2.46] for choledocholithiasis, and 1.31 [95% CI, 0.89-1.94] for acute cholangitis). The increased risk of the composite outcome associated with GLP-1RAs was more evident in patients aged >60 years, women, and 120 days after treatment initiation. Liraglutide, but not dulaglutide, was associated with an elevated risk.
GLP-1RAs might be associated with an elevated risk of biliary-related diseases compared to SGLT2is in Asian patients with type 2 diabetes.