Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used for metabolic disorders such as obesity and type 2 diabetes mellitus, have recently gained attention for potential benefits in patients with chronic migraine (CM), particularly among those with comorbid obesity.¹ Although proposed mechanisms extend beyond weight reduction, these effects remain incompletely understood.¹ At the AAN Annual Meeting 2026, Dr. Vitoria Acar from the University of Sao Paulo, Brazil, presented real-world evidence demonstrating that GLP-1 RAs initiation in adults with CM was associated with reduced healthcare utilization and lower intensity of migraine-related interventions and treatment escalation, highlighting the potential role of GLP-1 RAs in reducing migraine-related healthcare burden.¹

The real-world cohort study using the TriNetX^® Global Collaborative Network was conducted to evaluate healthcare utilization, acute treatment use, and preventive treatment escalation among adults with CM initiating GLP-1 RAs vs. those initiating topiramate, a commonly used first-line preventive therapy.¹ Adults with CM were identified using International Classification of Diseases (ICD)-10 coding and were stratified into two cohorts based on initiation of GLP-1 RAs or topiramate.¹ Patients in the GLP-1RA cohort had no prior exposure to topiramate, while those in the topiramate cohort had no prior exposure to GLP-1 RAs.¹

Baseline clinical characteristics were evaluated before and after propensity score matching to balance potential confounding factors between groups.¹ Clinical outcomes assessed included healthcare utilization such as emergency department (ED) visits and hospitalizations, migraine-related procedures including nerve block, acute migraine treatment use such as triptans, and preventive treatment escalation.¹ Patients with prior use of preventive treatment such as beta-blockers, antidepressants, valproate, calcitonin gene-related peptide (CGRP) monoclonal antibodies, and gepants, were excluded from the outcome analysis of preventive treatment escalation.¹

Baseline characteristics before cohort balancing showed that patients receiving GLP-1 RAs had a higher prevalence of overweight and obesity, higher baseline body mass index (BMI), and a greater burden of metabolic comorbidities, including type 2 diabetes mellitus, dyslipidemia, and sleep apnea.¹ This cohort also demonstrated higher baseline utilization of migraine-related procedures, including nerve blocks and onabotulinumtoxinA injections.¹ In addition, they had higher prescriptions of preventive migraine therapies such as CGRP monoclonal antibodies and beta blockers.¹

Following propensity score matching, GLP-1 RAs initiation was associated with a lower risk of healthcare utilization vs. topiramate.¹ Specifically, GLP-1 RA use was associated with a reduced risk of ED visits (risk ratio [RR]=0.90; 95% CI: 0.86-0.94) and hospitalization (RR=0.86; 95% CI: 0.81-0.91).¹ Consistent with these findings, GLP-1 RAs initiation also demonstrated reduced reliance on migraine-related procedures and acute treatments.¹ Patients receiving GLP-1 RAs had a lower risk of undergoing nerve block procedures (RR=0.87; 95% CI: 0.78-0.96).¹ Furthermore, GLP-1 RA users demonstrated a lower risk of triptan use (RR=0.87; 95% CI: 0.84-0.91), suggesting reduced need for acute migraine therapy.¹

In addition to reduced healthcare utilization, GLP-1 RA initiation was also associated with a lower likelihood of requiring additional preventive treatments vs. topiramate.¹ Compared with topiramate, GLP-1 RA initiation was associated with a lower risk of anti-CGRP use (RR=0.77; 95% CI: 0.69-0.85) and CGRP monoclonal antibodies initiation (RR=0.58; 95% CI: 0.52-0.65).¹ GLP-1 RA users also demonstrated a lower risk of initiating other preventive medication classes, including tricyclic antidepressants (TCAs) (RR=0.65; 95% CI: 0.55-0.77), serotonin-norepinephrine reuptake inhibitors (SNRIs) (RR=0.80; 95% CI: 0.64-0.99), and valproate (RR=0.52; 95% CI: 0.40-0.68).¹ In contrast, there was no significant difference between groups in the use of beta blockers as preventive therapy (RR=0.88; 95% CI: 0.76-1.01).¹

In summary, these findings from the real-world cohort study suggest that GLP1 RA initiation is associated with reduced healthcare utilization and lower need for both acute and preventive migraine-related treatments among adults with CM as compared with topiramate, indicating potential benefits in reducing treatment escalation and healthcare burden.¹ The study is limited by its observational design, and although baseline characteristics were balanced, residual confounding from unmeasured time-varying factors such as weight change, migraine severity, medication adherence, and dose titration cannot be excluded.¹ Further prospective studies are warranted to confirm these findings and clarify the role of GLP 1RAs in the management of CM.¹