Sodium-Glucose Cotransporter 2 Inhibitors and Reduced Fibromyalgia Risk in Patients With Diabetes

Background/Aim: Emerging evidence suggests that sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) may offer neuroprotective effects. This study aimed to compare the risk of new-onset fibromyalgia between diabetic patients starting SGLT2i versus those using GLP-1RA. Patients and Methods: A target trial emulation was conducted using the TriNetX Global Collaborative Network. Adult patients with type 2 diabetes mellitus starting use of SGLT2i or GLP-1RA were included, excluding those with prior fibromyalgia or psychiatric disorders. Propensity score-matching (1:1) was applied to demographics, comorbidities, laboratory data, and co-medications. The primary outcome was incidence of fibromyalgia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Results: After matching, 297, 937 patients per group were analyzed. During follow-up, fibromyalgia occurred in 6, 963 (2.3%) of SGLT2i users and 7, 855 (2.6%) of GLP-1RA users. SGLT2i use was associated with significantly lower fibromyalgia risk (HR=0.896, 95% CI=0.867-0.925). Findings remained robust in sensitivity analyses, including in 1-year (HR=0.884, 95% CI=0.855-0.914), 3-year (HR=0.880, 95% CI=0.850-0.912), and 5-year (HR=0.889, 95% CI=0.860-0.918) follow-up. Conclusion: In this large real-world cohort, SGLT2i use in diabetic patients was associated with a significantly reduced risk of fibromyalgia compared to GLP-1RA.