New research suggests a potential link between medications used for weight loss and diabetes and an increased risk of musculoskeletal issues, including tendon ruptures, gout, and osteoporosis. The findings, presented at a recent conference of the American Academy of Orthopaedic Surgery, highlight the need for closer monitoring of patients taking GLP-1 receptor agonists.
One study, led by Dr. Jad Lawad, an orthopaedic surgeon at the University of Texas, retrospectively analyzed data from 78,590 patients treated with GLP-1 agonists for diabetes or obesity, comparing them to a similarly matched control group. The five-year study, utilizing data from the TriNetX research network encompassing 70 U.S. Healthcare facilities, revealed a significant increase in tendon rupture risk among those taking the medications. Specifically, patients on GLP-1 agonists experienced a 55% higher risk of rotator cuff tendon rupture (2.4% versus 1.5% in the control group), a 49% increase in Achilles tendon rupture (0.3% versus 0.2%), and a 46% increase in pectoralis major tendon rupture (0.8% versus 0.5%). For obese patients with type 2 diabetes, the increased risks were 48%, 33%, and 53% respectively, with an additional 44% increase in quadriceps tendon rupture.
“These results support the idea of a prospective evaluation of the musculoskeletal adverse effects of GLP-1 analogues,” the authors wrote, emphasizing that even as the risk of tendon rupture remains low, the potential impact warrants further investigation. Researchers suggest several possible explanations for the observed link, including malnutrition due to appetite suppression and digestive side effects, potential muscle mass loss, a sudden increase in physical activity following weight loss, and possible drug interactions. Further studies are needed to explore these possibilities.
Increased Risk of Gout and Osteoporosis Also Noted
A separate retrospective case-control study compared 73,483 obese patients with type 2 diabetes treated with GLP-1 agonists to an equal number of untreated patients. After five years of follow-up, researchers found a significantly increased risk of osteoporosis in the treated group – 29% higher (4.1% versus 3.2%). The risk of gout was also elevated by 16% (7.4% versus 6.6%). There was no significant difference observed in the incidence of osteomalacia.
“Despite emerging hypotheses that this treatment is beneficial for musculoskeletal health, the long-term effects of exposure to GLP-1 analogues on bones and joints remain poorly understood,” the study authors stated. While recent mechanistic studies suggest a potential effect on calcium homeostasis and bone renewal, “real-world data are lacking,” they wrote. “Recent studies have demonstrated a potential protective effect but their lack of power does not make them generalizable.” Given the increasing prevalence of GLP-1 analogue prescriptions, the research team concludes that “physicians need to capture into account monitoring bone health.”
