GLP-1 RAs show signal of benefit in fibromyalgia

New research suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs), commonly used for diabetes and obesity, may hold therapeutic potential for patients with fibromyalgia.

Analysis of data from the TriNetX research network showed that among fibromyalgia patients, GLP-1 RA users had lower symptom burden compared with nonusers, as indicated by less opioid use (47.3 percent vs 59.9 percent; odds ratio [OR], 0.60; p<0.001) as well as reduced fatigue/malaise (21.8 percent vs 32.7 percent; OR, 0.576; p<0.001), pain (34.1 percent vs 43.2 percent; OR, 0.682; p<0.001), and need for ongoing fibromyalgia care (39.1 percent vs 55.7 percent; OR, 0.512; p<0.001). [EULAR 2025, abstract OP0281]

On the other hand, the disability outcome was similar and low in both GLP-1 RA user and nonuser cohorts (0.1 percent vs 0.1 percent; OR, 0.953; p=0.827).

First study author Dr Nouran Eshak from the Mayo Clinic Arizona, Scottsdale, Arizona, US, shared that the idea for investigating the role of GLP-1 RAs in fibromyalgia struck her while scrolling through a social media platform. She noted that comments from a great deal of patients who had used the medication were not about weight loss; they described something different: a remarkable reduction in food noise and inflammation. 

“I was actually pretty surprised… We have a signal or some sort of trend saying that GLP-1 RAs can be helpful in managing fibromyalgia and maybe even some other chronic pain conditions,” according to Eshak.

This is not unlikely, as there are published studies pointing to several ways in which GLP-1 RAs may help in pain management, including an upregulation of anti-inflammatory mediators such as IL-10, increase in endogenous opioid production (eg, beta-endorphins in the brain and spinal cord), downregulation of pro-inflammatory cytokines, and, as evidenced in chronic migraine research, direct suppression of allodynia and central sensitization. [J Headache Pain 2025;26:46; J Headache Pain 2021;22:86]

“The way that I see [it applied] in my practice is that if I have a patient with chronic pain or with fibromyalgia who have comorbidities such as diabetes, obesity, or obstructive sleep apnoea—for which GLP-1s are FDA-approved—I would encourage them to go to their primary care physician and [discuss] getting started on a GLP-1 RA,” Eshak said.

Nevertheless, she acknowledged the need to conduct further retrospective or prospective studies with validated outcome measures and to identify the phenotype of patients who do respond to GLP-1 RAs.

Study details

For the study, Eshak and colleagues established two cohorts of fibromyalgia patients, one that used GLP-1 RAs on at least two separate occasions and another that had no documented use of the medications. They used propensity scores to match users with nonusers, leading to the inclusion of 38,439 patients in each cohort.

The mean age was 55.3 years in the user cohort and 56.2 years in the nonuser cohort, with 82 percent of the patients overall being female. More than 50 percent of patients had diabetes mellitus and hypertension, around 23 percent had obstructive sleep apnoea, and roughly 29 percent had osteoarthritis. Outcomes were assessed over a 5-year follow-up period, beginning 1 year after the index event.

BMI and haemoglobin A1C levels improved from baseline in both groups. GLP-1 users saw their mean BMI drop from 37.3 to 35.3 kg/m² and their haemoglobin A1C improve from 7.2 percent to 6.9 percent. However, nonusers started out with lower BMI and haemoglobin A1C values and continued to show lower values at follow-up (from 35.4 to 34.1 kg/m²; from 6.9 percent to 6.7 percent) relative to users.

While based on large, real-world multicentre data across 104 healthcare organizations, the study was limited by its retrospective design, lack of fibromyalgia-specific validated symptom scales or outcome measures, and inability to account for several confounders, Eshak said.