Knee Surgery: Semaglutide vs Tirzepatide

A US database study found no statistically significant difference in short-term complications after total knee replacement between adults with type 2 diabetes prescribed semaglutide and those prescribed tirzepatide. After matching 415 people in each group, rates of medical complications, surgical complications, emergency visits and readmissions were similar through 90 or 180 days^[1].

This is useful comparative evidence, but it is not a randomized trial. The result does not prove that the two drugs are interchangeable around surgery, nor does it answer whether either prescription should be continued or paused for a particular operation. That decision still belongs with the surgical and anesthesia teams.

How the comparison was built

Researchers used the TriNetX national research network to identify adults with type 2 diabetes who underwent primary total knee arthroplasty between June 2022 and December 2024. Total knee arthroplasty is the clinical term for knee replacement. Eligible patients had an active semaglutide or tirzepatide prescription within the 90 days before surgery^[1].

The team used propensity-score matching, a statistical method that builds comparison groups with similar measured characteristics. Matching covered age, sex, race, body mass index, hemoglobin A1c, other illnesses and concurrent diabetes medicines. It produced 830 patients in total, split into 415 matched pairs^[1]. This method reduces obvious imbalance, but it cannot remove differences that were absent or poorly recorded in the database.

What the study found

At 90 days, the odds ratio for the combined medical-complication outcome was 1.122 for semaglutide relative to tirzepatide, with a 95% confidence interval from 0.736 to 1.710. At 180 days, the odds ratio for combined surgical complications was 1.632, with a confidence interval from 0.845 to 3.152. Both intervals crossed 1, and neither comparison was statistically significant^[1].

The individual outcomes were also statistically similar. The list included heart attack, stroke, pneumonia, sepsis, pulmonary embolism, deep-vein thrombosis, acute kidney injury, urinary infection, surgical-site infection, periprosthetic joint infection, wound separation, death and revision surgery. Emergency-department visits or readmissions did not differ significantly at either 90 or 180 days^[1]. Our tirzepatide safety page covers risks beyond this surgical window.

No significant difference does not mean identical risk. Several events were uncommon, which left wide confidence intervals and limited precision. For surgical-site infection, for example, the reported odds ratio was 1.726 but the confidence interval ran from 0.782 to 3.810^[1]. The study could not rule out a clinically meaningful difference in either direction for every rare event.

Why this does not settle perioperative use

The paper's conclusion says its findings support continued perioperative use of either agent in this population^[1]. That sentence needs a boundary. The analysis classified exposure from prescription records within 90 days before surgery; it did not randomly assign a continuation strategy, compare stop dates or document each patient's final preoperative dose. It therefore cannot determine the safest timing for an individual patient.

Current US prescribing information adds a separate anesthesia concern. The Ozempic label says semaglutide delays gastric emptying and reports pulmonary aspiration during general anesthesia or deep sedation in patients receiving GLP-1 receptor agonists. It tells patients to inform healthcare providers about planned procedures^[2]. The Mounjaro label carries the same warning for tirzepatide^[3]. Aspiration means stomach contents enter the airway or lungs.

That labeled warning is not evidence that one of these two drugs is safer around knee replacement. It explains why the absence of a complication difference in a retrospective database cannot replace a preoperative assessment. Symptoms, dose timing, anesthesia plan and other medical conditions can change the decision. See the broader semaglutide safety summary for label-based context.

What the study can tell us

For adults with type 2 diabetes already represented in this network, the study did not detect a short-term outcome gap between the two prescription groups after matching. That is more informative than comparing raw, unmatched records. It also gives researchers event estimates that can help size future studies^[1].

The finding should not be extended to people taking these medicines only for obesity, to other operations, or to patients with different health profiles. It also compares semaglutide with tirzepatide rather than comparing either drug with no GLP-1-class treatment. It cannot show whether the class improves or worsens knee-replacement outcomes overall.

What we still do not know

A randomized study would need to define continuation and withholding strategies, record the last dose precisely, and track both aspiration-related events and surgical recovery. Larger samples would improve estimates for uncommon outcomes such as periprosthetic infection or death. Longer follow-up would also clarify revision risk beyond six months.

For now, the narrow conclusion is the reliable one: this matched analysis found similar short-term outcomes between the two drug groups, with limited precision for rare events. Anyone preparing for knee replacement should give the full medication list to the surgeon and anesthesia team. Do not change a prescribed tirzepatide or semaglutide schedule without their guidance.

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