Efficacy of prophylactic ursodeoxycholic acid in preventing gallstone formation after metabolic bariatric surgery: an updated systematic review and meta-analysis of randomized controlled trials

Rapid weight loss following Metabolic bariatric surgery (MBS) is associated with an increased risk of developing de novo gallstone formation. We aimed to evaluate the efficacy of prophylactic ursodeoxycholic acid (UDCA) in preventing gallstone formation and reducing gallstone-related outcomes after MBS. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following the PRISMA guidelines through PubMed/MEDLINE, Cochrane, Embase, Scopus, Google Scholar, and clinicaltrials.gov. The primary outcome was gallstone formation at 12–24 months, while symptomatic gallstones and cholecystectomy incidence were secondary outcomes. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis was conducted according to UDCA dose, duration of administration, and the type of operation. Meta-regression was performed to assess the effect of age and baseline BMI on gallstone formation. I 2 and Cochrane Q p-value were used to assess the heterogeneity of the studies. Ten RCTs, including 3,575 participants, were included. Prophylactic UDCA reduced the incidence of gallstone formation by 67% at 12–24 months, and 73% at 6 months, while symptomatic gallstones were reduced by 70%. No statistically significant difference was found in the cholecystectomy rates. Subgroup analysis showed that UDCA doses of 500–600 mg daily administered for 6–12 months were effective, with no significant differences in gallstone formation between surgical procedures. Meta-regression analysis showed a slight increase in gallstone risk with age and a slight decrease with higher BMI, although neither relationship reached statistical significance. Prophylactic UDCA may be an effective preventive measure for gallstone formation in MBS patients, however additional studies are needed to assess its effect on cholecystectomy. The systematic review was registered in PROSPERO under registration number CRD420251004594.