New data suggest a link between using GLP-1 receptor agonists (GLP-1 RAs) and a significantly higher risk for tendon ruptures, primarily tears involving the rotator cuff, Achilles, and pectoralis major tendons in patients with obesity. The data was presented in a poster at the American Academy of Orthopaedic Surgeons Annual Meeting.

Over 5 years, in patients with obesity (BMI over 30), use of GLP-1 RAs was associated with higher risks for rotator cuff rupture (2.4% vs 1.5%; hazard ratio [HR], 1.55; P < .001), Achilles tendon rupture (0.3% vs 0.2%; HR, 1.49; P = .004), and pectoralis major rupture (0.8% vs 0.5%; HR, 1.46; P < .001).

In patients with both type 2 diabetes and obesity, GLP-1 RA use was associated with higher rates of rotator cuff (HR, 1.48; P < .001), peroneal (HR, 1.33; P = .044), pectoralis major (HR, 1.46; P = .006), Achilles tendon (HR, 1.53; P < .001), and quadriceps tendon ruptures (HR, 1.44; P = .001).

“These findings warrant prospective evaluation of potential musculoskeletal adverse effects of GLP-1 agonists,” wrote the authors, led by Jad Lawand, MS, a medical student at the University of Texas Medical Branch in Galveston, Texas. 

Researchers conducted a retrospective cohort study using the TriNetX Research Network, which contains electronic health record data from more than 70 large healthcare organizations across the US. Patients prescribed GLP-1 RAs were matched 1:1 with nonusers (n = 78,590 per group) using propensity scores based on age, sex, BMI, race, diabetes status, cholesterol levels, and statin use, “which has previously been associated with tendon ruptures,” Lawand noted.

Results Consistent When Patients With Obesity Had Diabetes

The researchers separately analyzed patients with obesity and patients with type 2 diabetes plus obesity because diabetes is also the initial indication for the medicines. 

“We found that our results were consistent in patients who are obese and also diabetic. Their risks of tendon ruptures when on these medications are higher,” Lawand told Medscape Medical News.

Lawand pointed out that it’s important to remember the risk for major tendon rupture is low. “Your overall risk is still less than 1% for most of these tears,” he said. “But it is 1.5 times higher than patients who are not on these medicines.”

The strength of the study is the sample size, Lawand said, “and that we could control for statin use and break it down by people who have diabetes.”

Theories on the Connection

Lawand said the researchers have several theories as to why the GLP-1 RAs are linked to increased tendon tear risk. One is that the medications suppress appetite and can lead to gastroparesis, which can interfere with digestion. “They can have malnutrition secondary to taking these medicines, and the malnutrition can contribute to some of our findings,” Lawand said.

A second theory is that because substantial weight loss is likely to reduce muscle mass, it can contribute to strain on tendons. It may also be that people losing weight rush to increase activity, Lawand said. “If they’re not maintaining a supervised physical activity program, that can lead to ruptures. Those are future directions for research.”

Alexander Sah, MD, co-director of the Outpatient Joint Replacement Program at the Institute for Joint Restorationin Fremont, California, said the study will help patients and physicians discuss choices as the number of people taking the medications climbs. 

“GLP-1s are so prevalent, and we don’t really know a lot about them, and it’s good for people to be aware about potential side effects,” Sah said.

In orthopedics, patients who are taking other medications that may weaken tendons need to be aware of the potential side effects of GLP-1s so they are not layering them on, Sah said. 

Further research may determine the biological reason for the link between GLP-1s and tendon tears, but for now it’s a mystery, he said.

Physicians and individual patients should weigh the risks of potential tendon tears against the potential benefits of weight loss with GLP-1s, Sah said. “Maybe there’s a familial history of tendon injuries, or they tore their quadriceps skiing — maybe those patients would think twice about using a medication like this,” Sah said.

Lawand and Sah reported having no relevant financial relationships.

Marcia Frellick is an independent, Chicago-based healthcare journalist and a regular contributor to Medscape.