Research Summary

Semaglutide vs Tirzepatide Shows Similar Outcomes After TKA in Adults With T2DM

Edited by:
Anthony Calabro, MA

Key Highlights

  • Semaglutide and tirzepatide were associated with statistically similar 90-day medical complication rates after primary total knee arthroplasty.
  • No significant difference in 180-day surgical complications was observed between the treatment cohorts.
  • Emergency department visits and readmissions were comparable at 90 and 180 days.
  • Low event counts for several outcomes limited the precision of the estimates.

Semaglutide and tirzepatide were associated with similar short-term postoperative safety and healthcare utilization among adults with type 2 diabetes mellitus (T2DM) undergoing primary total knee arthroplasty (TKA), according to a retrospective, propensity score-matched cohort study published online in The Knee. No significant differences were identified in composite medical complications, surgical complications, emergency department visits, or readmissions.

The researchers used the TriNetX national research network database to identify adults with T2DM who underwent primary TKA between June 1, 2022, and December 31, 2024. Eligible patients had an active prescription for semaglutide, a glucagon-like peptide-1 receptor agonist, or tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, within 90 days before surgery.

Investigators conducted 1:1 propensity score matching based on age, sex, race, body mass index, hemoglobin A1c, comorbidity burden, and concurrent diabetes medication use. The analysis included 415 matched pairs, for a total of 830 patients. Medical complications, surgical complications, and healthcare utilization were evaluated through 90 and 180 days using logistic regression to estimate odds ratios (ORs) and 95% CIs.

Study Findings

The risk of 90-day medical complications did not differ significantly between the semaglutide and tirzepatide cohorts (OR, 1.122; 95% CI, 0.736-1.710; P=.591). Similarly, the groups had no significant difference in surgical complications through 180 days (OR, 1.632; 95% CI, 0.845-3.152; P=.141).

Individual postoperative events were also statistically similar between the groups. These outcomes included myocardial infarction, stroke, pneumonia, sepsis, pulmonary embolism, deep vein thrombosis, periprosthetic joint infection, wound dehiscence, mortality, and revision surgery. No significant differences were observed for acute kidney injury (OR, 0.867; 95% CI, 0.417-1.801; P=.701), urinary tract infection (OR, 1.562; 95% CI, 0.863-2.827; P=.138), or surgical site infection (OR, 1.726; 95% CI, 0.782-3.810; P=.172).

Emergency department visits and/or hospital readmissions were comparable at 90 days (OR, 0.775; 95% CI, 0.570-1.052; P=.102) and 180 days (OR, 0.887; 95% CI, 0.672-1.170; P=.397).

Clinical Implications

According to the study authors, the findings support the continued perioperative use of either semaglutide or tirzepatide among patients with T2DM undergoing primary TKA. The similar short-term complication and utilization profiles may inform perioperative management of patients receiving these medications. Several outcomes occurred infrequently in both treatment groups, limiting the precision of the estimates.

Expert Commentary

“These findings support continued perioperative use of either agent in T2DM patients undergoing TKA,” the researchers concluded.

Reference
Wu KA, Choudhury A, Wu JA, et al. Postoperative outcomes after total knee arthroplasty in type 2 diabetes mellitus patients receiving semaglutide versus tirzepatide: a propensity score-matched national research network analysis. The Knee. Published online September 11, 2026. doi:10.1016/j.knee.2026.10463