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Peer-reviewedCC BYEuropean journal of orthopaedic surgery & traumatology : orthopedie traumatologie

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

  1. 1School of Medicine, Case Western Reserve University, Cleveland, USA.
  2. 2Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, USA.
  3. 3Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, USA. [email protected].

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 0.99; 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.

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BibTeX
@article{davis2026dual,
  title = {{Dual GIP/GLP-1 receptor agonist versus selective GLP-1 receptor agonist in patients undergoing primary total knee or hip arthroplasty.}},
  author = {Spencer C Davis and Shlok V Patel and Shane Fletcher and John P McLaughlin and Matthew E Deren and Nicolas S Piuzzi},
  journal = {European journal of orthopaedic surgery \& traumatology : orthopedie traumatologie},
  year = {2026},
  month = oct,
  doi = {10.1007/s00590-026-05000-9},
  url = {https://europepmc.org/article/MED/42905201},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Dual GIP/GLP-1 receptor agonist versus selective GLP-1 receptor agonist in patients undergoing primary total knee or hip arthroplasty.
AU  - Spencer C Davis
AU  - Shlok V Patel
AU  - Shane Fletcher
AU  - John P McLaughlin
AU  - Matthew E Deren
AU  - Nicolas S Piuzzi
PY  - 2026
DA  - 2026/10/21
JO  - European journal of orthopaedic surgery & traumatology : orthopedie traumatologie
DO  - 10.1007/s00590-026-05000-9
UR  - https://europepmc.org/article/MED/42905201
AB  - 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.
SN  - 1633-8065
SN  - 1432-1068
ER  -