Dual GIP/GLP-1 receptor agonist versus selective GLP-1 receptor agonist in patients undergoing primary total knee or hip arthroplasty

This is the authors' abstract. We don't add key points for this paper.

Purpose Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, whereas semaglutide is selective for the GLP-1 receptor. We compared post-operative outcomes after primary total knee or hip arthroplasty (TKA/THA) between patients prescribed tirzepatide and those prescribed semaglutide. Methods A retrospective cohort study was performed using the TriNetX US Collaborative Network. Adults undergoing primary TKA or THA with at least two coded prescription fills for tirzepatide or semaglutide within six months of surgery were identified, and patients taking both agents were excluded. Cohorts were propensity score matched 1:1 (2,858 per group, all standardized differences below 0.05). Odds ratios (OR) with 95% confidence intervals (CI) were calculated at 90 days, 1 year, and 2 years. Results Of 669,698 patients who underwent primary TKA or THA, 8,797 (1.3%) had ≥ 2 tirzepatide or semaglutide prescriptions. At 90 days and 1 year, no surgical, medical, or implant-related outcome differed significantly. At 2 years, tirzepatide exposure was associated with lower odds of mechanical complications (OR 0.64, 95% CI 0.42 to 0.96) and periprosthetic joint infection (PJI) (OR 0.64, 95% CI 0.41 to 0.99; P = .048). Reoperation did not differ significantly (OR 0.68, 95% CI 0.43 to 1.08). Conclusion Tirzepatide and semaglutide prescriptions were associated with similar 90 day and 1 year outcomes, while tirzepatide was associated with lower mechanical complications and PJI at 2-years. These preliminary associations warrant further investigation in larger cohorts to improve precision and clarify their clinical relevance.