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

Sep 24, 2026

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Tirzepatide, a dual GIP and GLP-1 receptor agonist, was compared with semaglutide, a selective GLP-1 receptor agonist, for postoperative outcomes in patients undergoing primary total knee arthroplasty (TKA) or total hip arthroplasty (THA). A retrospective propensity score–matched analysis used the TriNetX US Collaborative Network to evaluate patients with prescription fills for one agent within six months of surgery. At 90 days and 1 year, no significant surgical, medical, or implant-related differences were found, while 2-year tirzepatide exposure showed lower odds of mechanical complications and periprosthetic joint infection (PJI), without significant changes in reoperation.

LanguageEnglish

CategoryHealthcare

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Pages18

Reading Time45 min

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Purpose

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Study design and matching

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Dual GIP/GLP-1 Receptor Agonist Versus Selective GLP-1 Receptor Agonist in Patients Undergoing Primary Total Knee or Hip Arthroplasty Spencer C Davis Case Western Reserve University Shlok V Patel Cleveland Clinic Shane Fletcher Case Western Reserve University John P McLaughlin Cleveland Clinic Matthew E Deren Cleveland Clinic Nicolas S Piuzzi Cleveland Clinic Research Article Keywords: tirzepatide, semaglutide, GLP-1 receptor agonist, total knee arthroplasty, total hip arthroplasty, periprosthetic joint infection Posted Date: September 4th, 2026 DOI: [https://doi.org/10.21203/rs.3.rs-10744245/v1](https://doi.org/10.21203/rs.3.rs-10744245/v1) License: 􀁱 􀅏 This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Additional Declarations: Competing interest reported. Spencer C. Davis, Shlok V. Patel and Shane Fletcher declare they have no competing interests. John P. McLaughlin has the following disclosures, none related to the present study: consultant for Zimmer Biomet, Smith and Nephew, and OrthAlign. Matthew E. Deren has the following disclosures, none related to the present study: paid speaker for Brasseler; stock options in ROM Technologies; governing board of The Journal of Knee Surgery. Nicolas S. Piuzzi has the following disclosures, none related to the present study: grants or contracts from Osteal Therapeutics, Peptilogics, RegenLab, Signature Orthopedics, Zimmer and Stryker; consulting fees from Zimmer, Pacira Pharmaceutical and Stryker; editorial board member or leadership role with JBJS, the American Association of Hip and Knee Surgeons and the Orthopaedic Research Society. 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 postoperative 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. Introduction Total knee and total hip arthroplasty (TKA/THA) are among the most frequently performed operations worldwide, and utilization has continued to rise across international health systems [ 1, 2] . In the United States they are among the most common and reliable orthopaedic procedures [3], and their effectiveness has prompted calls for arthroplasty to be recognized as an essential surgical service worldwide [4] . More than 7 million Americans currently live with a knee or hip replacement, and the annual volume of both procedur

FAQs

What was the main purpose of comparing tirzepatide with semaglutide in arthroplasty patients?

To evaluate whether postoperative outcomes after primary TKA or THA differ between patients prescribed tirzepatide versus those prescribed semaglutide.

How was the study conducted and how were patient groups formed?

A retrospective cohort study used the TriNetX US Collaborative Network, identifying adults who had at least two coded prescription fills for one drug within six months of surgery, excluding patients taking both agents, and then performing 1:1 propensity score matching.

What were the key findings at 90 days, 1 year, and 2 years?

At 90 days and 1 year, no surgical, medical, or implant-related outcomes differed significantly. At 2 years, tirzepatide was associated with lower odds of mechanical complications and periprosthetic joint infection (PJI).

What does the conclusion suggest about whether these medications should be treated as equivalent?

It suggests they should not be presumed equivalent, because dual GIP/GLP-1 agonism versus selective GLP-1 agonism may carry clinical relevance despite similar short-term outcomes.

Sep 24, 2026

Uploaded by Franzy