Postoperative outcomes after total knee arthroplasty in type 2 diabetes mellitus patients receiving semaglutide versus tirzepatide: a propensity score-matched national research network analysis

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Abstract

[BACKGROUND] Semaglutide (GLP-1 receptor agonist) and tirzepatide (dual GIP/GLP-1 agonist) are increasingly prescribed to adults with type 2 diabetes mellitus (T2DM) undergoing total knee arthroplasty (TKA). Whether short-term postoperative outcomes differ between these agents was unknown. [METHODS] This was a retrospective cohort study using the TriNetX research network database. Adults with T2DM who underwent primary TKA between June 1, 2022, and December 31, 2024, and had an active prescription for semaglutide or tirzepatide within 90 days preoperatively were eligible. 1:1 propensity score matching was conducted on age, sex, race, body mass index, hemoglobin A1c, comorbidity burden, and concurrent diabetes medication use, yielding 415 matched pairs. Outcomes through 90 and 180 days included medical complications, surgical complications, and healthcare utilization. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression. [RESULTS] After matching (n = 830), there were no differences in 90-day medical complications (OR 1.122, 95% CI 0.736-1.710; P = 0.591) or 180-day surgical complications (OR 1.632, 95% CI 0.845-3.152; P = 0.141) between semaglutide and tirzepatide cohorts. Individual events, including myocardial infarction, stroke, pneumonia, sepsis, pulmonary embolism, deep vein thrombosis, acute kidney injury (OR 0.867, 95% CI 0.417-1.801; P = 0.701), urinary tract infection (OR 1.562, 95% CI 0.863-2.827; P = 0.138), surgical site infection (OR 1.726, 95% CI 0.782-3.810; P = 0.172), periprosthetic joint infection, wound dehiscence, mortality, and revision-were statistically similar (all P > 0.05). Emergency department visits and/or readmissions were comparable at 90 days (OR 0.775, 95% CI 0.570-1.052; P = 0.102) and 180 days (OR 0.887, 95% CI 0.672-1.170; P = 0.397). Several outcomes had low event counts in both groups, limiting precision. [CONCLUSION] In a large, propensity-matched national cohort of primary TKA, semaglutide and tirzepatide demonstrated similar short-term safety and utilization profiles. These findings support continued perioperative use of either agent in T2DM patients undergoing TKA.

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