This study was carried out with the goal of consolidating data from clinical trials to investigate the safety concerns related to Tirzepatide, specifically focusing on pancreatitis and gallbladder or biliary ailment, in individuals with obesity and type 2 diabetes (T2D).

A systematic exploration was carried out across 3 databases— Cochrane Library, PubMed, and Embase—to identify randomized controlled trials (RCTs) that compared Tirzepatide with either a placebo or active hypoglycemic drugs in obesity and T2D subjects. The assessment of heterogeneity involved Cochran's Q test and I2 value, and a fixed effects model was used for the estimation of the safety of Tirzepatide.

Examination of the safety endpoints, such as biliary disorders and cholelithiasis, cholecystitis, pancreatitis, and the composite of gallbladder or biliary illness (encompassing biliary ailments, other gallbladder disorders, cholecystitis, and cholelithiasis) was done.

In this systematic review and meta-analysis, 9 trials involving 9871 volunteers (6828 in the Tirzepatide arm and 3043 in the control arm) meeting pre-specified criteria were incorporated. In comparison to control groups comprising basal insulin (Degludec or Glargine), selective glucagon-like peptide-1 receptor agonists (GLP1-RA) like Semaglutide or Dulaglutide once a week, and placebo, Tirzepatide did not show a substantially elevated pancreatitis risk (Risk ratio [RR] 1.46; I2 = 0.0%).

However, there was a significant association between Tirzepatide and the composite of biliary disease or gallbladder in comparison with the placebo or basal insulin (RR 1.97; I2 = 0.0%), although no significant association was found with the risk of other biliary diseases, cholecystitis, or cholelithiasis.

Tirzepatide exhibited a favorable safety profile regarding pancreatitis risk. However, the heightened risk of the combined occurrence of gallbladder or biliary diseases observed in RCTs underscored the necessity for careful consideration by healthcare practitioners in clinical practice.