Do GLP-1 Weight Loss Drugs Affect Bone Healing After Leg Fracture Surgery?

Large retrospective study of GLP-1 RA users undergoing leg fracture surgery found clinical outcomes with two-year follow-up, though the effects on fracture healing remain controversial.

Pereira, Daniel E et al.·Injury·2025·Moderate EvidenceRetrospective Cohort
RPEP-13020Retrospective CohortModerate Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Retrospective Cohort
Evidence
Moderate Evidence
Sample
N=275970
Participants
Patients undergoing lower extremity fracture surgery, comparing GLP-1 users to non-users

What This Study Found

Large propensity-matched retrospective analysis compared perioperative GLP-1 RA users with non-users following lower extremity fracture fixation with two-year follow-up.

Key Numbers

275,970 patients analyzed. 6,125 propensity-matched pairs. Matched on age, sex, tobacco, diabetes, hypertension, hyperlipidemia, heart disease, lung disease, and BMI. Higher nonunion rate in GLP-1 group at 1 year.

How They Did This

Retrospective propensity-matched cohort study from a large multicenter database, comparing GLP-1 RA users (within one year of surgery) versus non-users after lower extremity fracture fixation.

Why This Research Matters

Millions of GLP-1 RA users may need fracture surgery. Knowing whether these drugs impair or help bone healing is critical for surgical planning and medication management decisions.

The Bigger Picture

This is one of the largest studies addressing the GLP-1 RA and bone health question, which is increasingly relevant as these drugs are prescribed to a broader population that includes elderly and fracture-prone patients.

What This Study Doesn't Tell Us

Retrospective design — cannot prove causation. GLP-1 RA users may differ from non-users in ways not captured by propensity matching. Specific fracture types and healing metrics vary.

Questions This Raises

  • ?Should GLP-1 RAs be paused before fracture surgery?
  • ?Do the potential bone-protective effects of weight loss counterbalance any direct drug effects on bone healing?

Trust & Context

Key Stat:
275,970 patients matched One of the largest studies examining GLP-1 RA effects on fracture healing outcomes
Evidence Grade:
Large retrospective cohort study with propensity matching — strong for observational data but cannot replace a randomized trial for establishing causation.
Study Age:
Published in 2025, addressing a timely concern as GLP-1 RA prescribing continues to expand rapidly.
Original Title:
Perioperative glucagon-like Peptide-1 receptor agonist use and clinical outcomes following lower extremity fracture fixation: A large retrospective cohort study with two year follow up.
Published In:
Injury, 56(11), 112746 (2025)
Database ID:
RPEP-13020

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-ControlFollows or compares groups over time
This study
Cross-Sectional / Observational
Case Report / Animal Study

Looks back at existing records to find patterns.

What do these levels mean? →

Frequently Asked Questions

Do GLP-1 drugs weaken bones?

The evidence is controversial. Some studies suggest GLP-1 RAs may have bone-protective effects, while others raise concerns about fracture healing. This large study provides important real-world data on actual surgical outcomes.

Should I stop my GLP-1 medication before fracture surgery?

This is a decision to make with your orthopedic surgeon and endocrinologist based on the latest evidence. This study helps inform that discussion by providing outcome data from a large patient population.

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Cite This Study

RPEP-13020·https://rethinkpeptides.com/research/RPEP-13020

APA

Pereira, Daniel E; Tummala, Sri; Mittal, Mehul M; Obey, Mitchel; Berkes, Marschall B; McAndrew, Christopher M; Wilson, Jenna L. (2025). Perioperative glucagon-like Peptide-1 receptor agonist use and clinical outcomes following lower extremity fracture fixation: A large retrospective cohort study with two year follow up.. Injury, 56(11), 112746. https://doi.org/10.1016/j.injury.2025.112746

MLA

Pereira, Daniel E, et al. "Perioperative glucagon-like Peptide-1 receptor agonist use and clinical outcomes following lower extremity fracture fixation: A large retrospective cohort study with two year follow up.." Injury, 2025. https://doi.org/10.1016/j.injury.2025.112746

RethinkPeptides

RethinkPeptides Research Database. "Perioperative glucagon-like Peptide-1 receptor agonist use a..." RPEP-13020. Retrieved from https://rethinkpeptides.com/research/pereira-2025-perioperative-glucagonlike-peptide1-receptor

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.