Dual GIP/GLP-1 Receptor Agonist Versus Selective GLP-1 Receptor Agonist in Patients Undergoing Primary Total Knee or Hip Arthroplasty

Tirzepatide may be associated with lower odds of mechanical complications and infections compared to semaglutide in patients undergoing major joint surgeries, but the clinical relevance of these findings should be considered cautiously.

Summary and findings

This study compared post-operative outcomes in patients undergoing primary total knee or hip arthroplasty who were prescribed tirzepatide versus semaglutide. The analysis involved a retrospective cohort of 8,797 patients with at least two prescriptions for either medication. At two years, tirzepatide was associated with lower odds of mechanical complications and periprosthetic joint infection compared to semaglutide.

Abstract

Abstract 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 0.999; 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 2-year mechanical complications and PJI. The distinction between dual GIP/GLP-1 agonism and selective GLP-1 agonism may therefore carry clinical relevance, and these agents should not be presumed equivalent.

Limitations

Not reported in abstract.

Elsewhere in the Tirzepatide corpus