A Shot in the Dark: The Paradoxical Effects of GLP-1 Receptor Agonists on Rotator Cuff Disease and Surgical Outcomes

Abstract

Background: Degenerative rotator cuff disease (RCD) is a common cause of shoulder pain and functional impairment in adults and frequently requires surgical intervention when conservative management fails. Obesity (BMI ≥30) and type 2 diabetes mellitus (T2DM) are established risk factors for rotator cuff pathology and are associated with tendon degeneration, impaired healing, and poorer postoperative outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for both obesity and T2DM due to their effectiveness in promoting weight loss and improving glycemic control. Emerging evidence suggests a potential paradoxical relationship in which GLP-1RA therapy may increase the incidence of native shoulder pathology while also demonstrating protective perioperative effects.

Objective: To evaluate whether GLP-1RA therapy influences the risk of degenerative rotator cuff disease and postoperative outcomes in adults with obesity and/or T2DM.

Design: Systematic evidence review.

Methods: A literature search was conducted using the National Library of Medicine databases PubMed and Ovid MEDLINE (March 2026) to identify studies evaluating GLP-1RA therapy and rotator cuff and tendon pathology among patients with obesity or type 2 diabetes mellitus. MeSH terms were applied across three domains: the primary intervention (“Glucagon-Like Peptide 1” OR “Glucagon-Like Peptide-1 Receptor Agonists”), the targeted population (“Obesity” OR “Diabetes Mellitus” OR “Diabetes Mellitus, Type 2”), and the clinical outcome (“Rotator Cuff Injuries” OR “Tendinopathy” OR “Rotator Cuff” OR “Arthroscopy” OR “Shoulder Pain” OR “Tendon Injuries” OR “Postoperative Complications” OR “Shoulder Injuries”), with all three domains joined by the Boolean operator AND. The combined search yielded 56 records. After applying predefined inclusion criteria, four retrospective cohort studies were included in the final analysis. Critical appraisal considered study methodology, effect sizes, statistical significance, and clinical relevance.

Results: Across the included studies, GLP-1RA therapy demonstrated divergent effects on RCD, with modest increases in incident native shoulder pathology but neutral to potentially beneficial outcomes in postoperative rotator cuff repair populations. Davis et al. reported a more than twofold increased risk of adhesive capsulitis among obese patients without diabetes (HR 2.47, NNH 83 over 5 years). Smaller absolute risk increases were also observed for atraumatic rotator cuff tears and glenohumeral osteoarthritis in patients with obesity and/or T2DM. Bergstein et al. similarly found an increased incidence of adhesive capsulitis among patients with T2DM, along with a higher likelihood of operative intervention, particularly manipulation under anesthesia (OR 1.07; ARI 0.9%; NNH 111). In contrast, perioperative studies demonstrated unexpectedly favorable surgical outcomes among GLP-1RA users undergoing arthroscopic rotator cuff repair (ARCR). Seddio et al. reported that preoperative semaglutide use was associated with significantly fewer postoperative adverse events (11% vs 27.4%; ARR 16.4%; NNT 6) and lower retear rates at two years. A separate matched-cohort analysis by Lauck et al. similarly found reduced 90-day hospital readmissions (2.7% vs 3.6%; OR 0.74) and fewer 2-year repeat rotator cuff repairs among GLP-1RA users, without an increase in postoperative complications.

Conclusion: GLP-1 receptor agonist therapy appears to exert context-dependent musculoskeletal effects in adults with obesity and/or T2DM. Chronic GLP-1RA use may modestly increase the risk of native shoulder pathology, particularly adhesive capsulitis and atraumatic rotator cuff tears, whereas GLP-1RA use in patients undergoing arthroscopic rotator cuff repair may reduce postoperative complications and retear rates. Interpretation is limited by retrospective study designs and potential confounding related to baseline metabolic disease and weight loss. Future prospective studies and randomized controlled trials are needed to clarify causal relationships and inform risk stratification and clinical decision-making regarding GLP-1RA therapy in patients at risk for rotator cuff disease.

Other

The author declares no conflicts of interest.

Acknowledgements

The author wishes to thank Michael A. Fotis, BS Pharm, for his mentorship and faculty guidance throughout the conception and development of this research.