Protective effects of SGLT2 inhibitors and GLP-1 receptor agonists on infection-related implant failure following ankle fracture ORIF: A global big data analysis.

Abstract

BackgroundPatients with type 2 diabetes (T2DM) undergoing ankle fracture open reduction and internal fixation (ORIF) face high risks of surgical site infection (SSI) and implant failure. This study evaluated whether preoperative use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improves these postoperative outcomes.MethodsUsing the TriNetX global database (2005-2025), we identified T2DM patients undergoing ankle fracture ORIF. Users of SGLT2is or GLP-1 RAs within 180 days before surgery were compared with non-users using 1:1 propensity score matching (PSM). The primary outcome was a 90-day composite of SSI or infection-related implant removal. Secondary outcomes included the 1-year composite and all-cause mortality.ResultsAfter PSM, 1289 users were compared with 1289 non-users. At 90 days, the composite infection-related outcome occurred in 1.45% of users versus 6.26% of non-users (HR 0.34, 95% CI 0.19-0.62; p < 0.001). At 1 year, the risk remained significantly lower in users (1.79% vs 11.92%; HR 0.42, 95% CI 0.25-0.72; p < 0.001). While 1-year mortality showed a downward trend in the primary cohort (HR 0.61, p = 0.1393), sensitivity analyses excluding dual-therapy users demonstrated a statistically significant survival advantage for single-agent users (HR 0.41, 95% CI 0.21-0.80; p = 0.007). Further analysis restricted to active users (30-day exposure) showed no observed instances of mortality or 1-year infection-related complications (both p < 0.001), although these findings should be interpreted cautiously given the small number of events.ConclusionsPreoperative use of SGLT2is or GLP-1 RAs was associated with a substantial reduction in infection-related implant failure and a lower risk of mortality, particularly when used as monotherapy or in closer proximity to surgery. These findings suggest that modern cardiometabolic agents may represent valuable components of preoperative optimization strategies in high-risk diabetic patients, although confirmation in prospective studies is warranted.