Migraine and Obesity: From Shared Mechanisms to Therapeutic Strategies

Migraine and obesity are highly prevalent, chronic conditions that frequently coexist, presenting a significant clinical and therapeutic challenge. Their relationship is multifactorial and bidirectional, albeit with more consistent evidence supporting obesity as a contributor to migraine than the converse, driven by shared biological mechanisms that include systemic low-grade inflammation, adipose-derived adipokines, metabolic dysfunction, and insulin resistance. These systemic disturbances converge on hypothalamic dysregulation and altered neuropeptide signaling, notably involving calcitonin gene-related peptide (CGRP), ultimately promoting trigeminovascular activation and migraine chronification. Clinically, excess body weight is associated with increased attack frequency, greater pain intensity, and higher disability, particularly in women of reproductive age. Conversely, migraine can indirectly influence factors contributing to weight gain, often compounded by psychological comorbidities. Management requires an integrated approach; traditional oral preventives that promote weight gain should be avoided, prioritizing sustainable lifestyle interventions alongside modern, weight-neutral or weight-reducing therapies. This article reviews the available evidence documenting the complex pathophysiological link between obesity and migraine, diagnostic and clinical implications across specific populations, and current management strategies. Emphasis is placed on novel therapeutic options, including CGRP-targeted agents and glucagon-like peptide 1 (GLP-1) receptor agonists, as well as future directions and unmet clinical needs in the management of comorbid migraine and obesity.