Longitudinal effects of CGRP ‐targeting migraine therapies on blood pressure and body mass index: A 12‐month retrospective analysis

Objective To compare blood pressure (BP) and body mass index (BMI) trajectories associated with individual calcitonin gene‐related peptide (CGRP)‐targeting migraine therapies versus matched CGRP‐unexposed controls. Background CGRP is a potent vasodilator with established roles in vascular homeostasis and metabolic regulation. Postmarketing surveillance identified BP elevations in erenumab‐treated patients, prompting a U.S. Food and Drug Administration label update; however, comparative longitudinal data across CGRP monoclonal antibodies and gepants remain limited. Real‐world evidence is needed to characterize medication‐specific cardiovascular and metabolic effects in clinical practice. Methods We conducted a retrospective cohort study using structured electronic health record data from the Jefferson Headache Center in Philadelphia, PA, USA (2018 to 2025). Adults initiating erenumab, fremanezumab, galcanezumab, atogepant, or preventive rimegepant were compared with propensity score‐matched patients receiving migraine care without CGRP‐targeting therapy. Twelve‐month systolic BP (SBP), diastolic BP (DBP), and BMI trajectories were evaluated. Results A total of 6361 patients were included (1892 controls; 4469 CGRP‐treated; 80.4% female; mean age 45.6 ± 15.3 years). Controls demonstrated a positive within‐group SBP trajectory (0.16 mmHg/month; 95% confidence interval [CI] 0.06 to 0.27) and BMI trajectory (0.022 kg/m 2 /month; 95% CI 0.004 to 0.040) but not DBP trajectory (0.06 mmHg/month; 95% CI −0.02 to 0.14). Among CGRP‐treated groups, only erenumab showed a positive within‐group SBP trajectory (0.11 mmHg/month; 95% CI 0.02 to 0.20); however, the difference in slope between erenumab and controls was not significant (−0.05 mmHg/month; 95% CI −0.19 to 0.09). Compared with controls, atogepant (−0.38 mmHg/month; 95% CI −0.61 to −0.15), fremanezumab (−0.27 mmHg/month; 95% CI −0.42 to −0.11), and galcanezumab (−0.31 mmHg/month; 95% CI −0.46 to −0.16) demonstrated more negative SBP trajectories. For DBP, only atogepant showed a more negative trajectory than controls (−0.18 mmHg/month; 95% CI −0.32 to −0.04). For BMI, both atogepant (−0.113 kg/m 2 /month; 95% CI −0.159 to −0.067) and erenumab (−0.031 kg/m 2 /month; 95% CI −0.053 to −0.008) had more negative trajectories compared to controls. Conclusion In this single‐center study, CGRP‐targeting therapies were not associated with greater BP increases than matched controls. Cardiometabolic trajectories varied by medication, with generally small BP differences and a robust BMI reduction with atogepant. These findings do not support a uniform adverse cardiometabolic class effect, though prospective studies with systematic monitoring are needed to confirm long‐term clinical significance.