What is the risk of ligament rupture in patients using Glucagon-like peptide-1 (GLP-1) receptor agonists, such as Byetta (exenatide) or Victoza (liraglutide)?

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Last updated: August 12, 2025View editorial policy

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Risk of Ligament Rupture with GLP-1 Receptor Agonists

There is currently no established association between GLP-1 receptor agonists and ligament rupture based on the available evidence. While GLP-1 receptor agonists have been associated with various adverse effects, ligament rupture is not among the documented risks in current guidelines or research.

Known Adverse Effects of GLP-1 Receptor Agonists

Gastrointestinal Effects

  • Most common adverse effects include nausea, vomiting, and delayed gastric emptying 1, 2
  • Increased risk of gastric retention even with prolonged fasting periods 1
  • Risk of regurgitation and pulmonary aspiration during anesthesia 1

Musculoskeletal Concerns

  • One case report described a bilateral, symmetrical, seronegative polyarthritis associated with liraglutide that resolved within one week of discontinuation 3
  • This isolated case suggests a potential mechanism mediated by GLP-1 receptor stimulation that could affect inflammatory processes 3
  • Recent comprehensive mapping of GLP-1RA effects found increased risk of arthritic disorders compared to usual care 4

Other Documented Adverse Effects

  • Increased risk of gastrointestinal disorders, hypotension, syncope, nephrolithiasis, interstitial nephritis, and drug-induced pancreatitis 4, 5
  • Contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 2

Clinical Implications

Risk Assessment

  • When considering GLP-1 receptor agonists, evaluate:
    • Baseline gastrointestinal function
    • Renal function (eGFR, urine albumin-to-creatinine ratio)
    • Cardiovascular parameters (heart rate, blood pressure) 2
  • No specific recommendation to assess ligament integrity before initiating therapy

Monitoring

  • Regular assessment of glycemic control, weight changes, GI symptoms, renal function, and cardiovascular parameters is necessary 2
  • No specific monitoring for ligament health is recommended in current guidelines

Clinical Perspective

While there is one case report of polyarthritis associated with GLP-1 receptor agonist use 3 and a large study showing increased risk of arthritic disorders 4, there is no specific evidence linking these medications to ligament rupture. The polyarthritis case resolved quickly after medication discontinuation, suggesting a reversible inflammatory mechanism rather than structural damage to ligaments.

The benefits of GLP-1 receptor agonists—including significant weight loss (5.8-14.7% reduction), improved glycemic control, and cardiovascular protection (13-26% reduction in major adverse cardiovascular events)—should be weighed against their known risks 2.

If a patient on GLP-1 receptor agonists develops joint pain or inflammation, consider temporary discontinuation of the medication to determine if symptoms resolve, as demonstrated in the case report 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Type 2 Diabetes

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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