Fibromyalgia Pain: The Next Frontier for GLP-1 RAs?

GLP-1 receptor agonists (RAs) improved pain, fatigue, and reduced opioid dependency in people with fibromyalgia, in recent data from a cohort study.1

“Fibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and a significant impact on quality of life. Management often relies on symptomatic treatments, including opioids and antidepressants, with varying efficacy and safety profiles. Emerging evidence suggests that GLP-1 RAs may have broader benefits beyond glucose regulation and weight loss, including potential analgesic and anti-inflammatory effects,” lead investigator Nouran Eshak MBChB, rheumatology fellow at Mayo Clinic, and colleagues wrote.1

Eshak and colleagues conducted a propensity-matched cohort analysis using the TriNetX research network. They compared patients with a documented diagnosis of fibromyalgia and the use of GLP-1 RAs on at least 2 separate occasions in cohort A (n = 46,409) to patients with fibromyalgia documented twice with no use of GLP-1 receptor agonists in cohort B (n = 716,185). They used propensity score matching to balance the groups for age, gender, comorbidities (including diabetes mellitus, hypertension, obstructive sleep apnea, other inflammatory and soft tissue disorders, osteoarthritis, ischemic heart disease, and hypothyroidism), hemoglobin A1c levels, body mass index (BMI) categories, and medication use (including opioid analgesics, non-opioid analgesics, non-steroidal anti-inflammatory drugs, and antidepressants), resulting in final cohorts of 38,439 patients each. Investigators assessed outcomes over a 5-year follow-up period, beginning 1 year after the index event, that included opioid use, fatigue, malaise, chronic pain, continued care for fibromyalgia, BMI and hemoglobin A1C levels.

Eshak and colleagues found that cohort A had a significantly lower risk of opioid use (based on documentation of any administration of opioid analgesics) than cohort B (odds ratio [OR], 0.600; risk difference, -12.6%; P <.001). Cohort A also had a lower prevalence of fatigue and malaise (OR, 0.576; risk difference, -10.8%; P <.001) and pain outcomes (OR, 0.682; risk difference, -9.1%; P<.001).1

In examining ongoing fibromyalgia care, cohort A had a reduced reliance on care (OR, 0.512; risk difference, -16.6%, P <.001), although investigators did not find any differences in risk of disability (OR, 0.953; risk difference, 0%, P = .827). They found that both cohorts had improvements in their BMI and hemoglobin A1c from baseline, but cohort B continued to demonstrate lower BMI and A1c values at follow-up, with a mean BMI of 34.1 kg/m² and A1c of 6.7% compared to Cohort A, which had a mean BMI of 35.3 kg/m² and A1c of 6.9%.

“This study supports the hypothesis that GLP-1 receptor agonists may reduce the symptom burden in fibromyalgia patients, particularly with regard to opioid dependency, fatigue, and pain. These findings suggest that GLP-1 receptor agonists could represent a novel therapeutic option in fibromyalgia management. Improvement in BMI, glucose control or other residual confounders may contribute to these outcomes. Further exploration through randomized controlled trials would be needed,” Eshak and colleagues concluded.1

A recent narrative review, led by Yongtao He, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, China, also found clinical and preclinical evidence supporting the use and underlying biological mechanisms of GLP-1 RAs to modulate 7 pain modalities, including inflammatory pain, osteoarthritis, visceral pain, neuropathic pain, diabetic neuropathy, cancer pain and headache.2

“Despite these promising findings, further research is necessary to establish their long-term efficacy, optimal dosing strategies, and potential synergistic interactions of GLP-1RAs with existing pain management therapies. Future clinical trials should aim to distinguish the direct analgesic effects of GLP-1RAs from their metabolic benefits and explore their broader applications in pain conditions. The ongoing exploration of new indications for GLP-1RAs further highlights their transformative potential in advancing medical treatments across diverse clinical fields,” Hao and colleagues wrote.2

REFERENCES

1. N. Eshak, A. Beltagy, I. Bazigh, et al. OP0281 EXPLORING GLP-1 AGONISTS EFFECTS IN FIBROMYALGIA PATIENTS: A PROPENSITY MATCHED ANALYSIS USING TriNetX DATABASE. Ann. Rheum. Dis. 2025;84:232-232. doi:https://doi.org/10.1016/j.ard.2025.05.291

2. ‌ He, Y., Xu, B., Zhang, M. et al. Advances in GLP-1 receptor agonists for pain treatment and their future potential. J Headache Pain 26, 46 (2025). https://doi.org/10.1186/s10194-025-01979-4