Braca Simone, Russo Cinzia Valeria, Stornaiuolo Antonio, Cretella Gennaro, Miele Angelo, Giannini Caterina, De Simone Roberto
Department of Neurological Sciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy.
Headache. 2025 Jun 17. doi: 10.1111/head.14991.
To assess whether glucagon-like-peptide-1 receptor (GLP-1R) agonists could serve as a novel prophylactic treatment for migraine in patients with obesity.
Increased intracranial pressure (ICP) is speculated to play a role in migraine mechanisms, as chronic migraine and idiopathic intracranial hypertension without papilledema (IIWHOP) are often clinically indistinguishable. These striking similarities suggest a deep pathogenetic link between the two conditions posing the hypothesis that control of ICP may be helpful in migraine treatment. The GLP-1R agonists have been shown to greatly reduce ICP. Notably, they have also been demonstrated to decrease calcitonin gene-related peptide expression in chronic migraine models.
This was a prospective, interventional, open-label, pilot cohort study, evaluating the effectiveness of liraglutide as an add-on treatment of unresponsive migraine in patients with obesity. We consecutively enrolled patients with high-frequency or chronic migraine and a body mass index (BMI) of >30 kg/m, and unresponsive to at least two preventive treatments. We excluded patients with papilledema, sixth nerve palsy, or pulsatile tinnitus, to rule out patients in which idiopathic intracranial hypertension could be clinically suspected. Liraglutide was administered 1.2 mg daily. The study was conducted from January to July 2024, with a 12-week follow-up period. The primary outcome of this study was the reduction of monthly days with headache after 12 weeks of treatment with liraglutide compared to baseline.
We enrolled 31 patients (26 females, five males, with a mean [standard deviation, SD] age of 44.9 [14.6] years). The mean (SD) monthly days with headache decreased from 19.8 (6.7) to 10.7 (7.7) days post-treatment. This change was significant with a mean difference of 9.1 days (95% confidence interval [CI] 5.41-12.84, p < 0.001, Cohen's d: 0.90). Conversely, BMI decreased slightly from a mean (SD) of 34.0 (2.3) to 33.9 (2.3) kg/m, and this change was not significant (mean difference = 0.1 kg/m, 95% CI -0.004 to 0.153 kg/m, p = 0.060, Cohen's d: 0.34). Analysis of covariance indicated that age, sex, and concomitant medications did not significantly influence headache frequency reduction (all p > 0.050). Simple linear regression analysis showed that BMI reduction did not significantly predict headache frequency reduction (β = -1.448, 95% CI -19.390 to 16.495, p = 0.870, R = 0.001), indicating no meaningful relationship between the two variables.
Our findings show that liraglutide may be effective in the treatment of unresponsive high-frequency or chronic migraine in patients with obesity, and that this effect is independent from weight loss. Although further studies are needed to clarify this topic, these findings generate the hypothesis that a derangement in ICP control may play a role in migraine pathogenesis and potentially represent a novel therapeutic target.
评估胰高血糖素样肽-1受体（GLP-1R）激动剂是否可作为肥胖患者偏头痛的一种新型预防性治疗方法。
推测颅内压升高（ICP）在偏头痛机制中起作用，因为慢性偏头痛和无视乳头水肿的特发性颅内高压（IIWHOP）在临床上往往难以区分。这些显著的相似性表明这两种情况之间存在深层的发病机制联系，提出了控制ICP可能有助于偏头痛治疗的假设。已证明GLP-1R激动剂可大幅降低ICP。值得注意的是，在慢性偏头痛模型中，它们还被证明可降低降钙素基因相关肽的表达。
这是一项前瞻性、干预性、开放标签的试点队列研究，评估利拉鲁肽作为肥胖患者难治性偏头痛附加治疗的有效性。我们连续纳入了高频或慢性偏头痛且体重指数（BMI）>30 kg/m²，且对至少两种预防性治疗无反应的患者。我们排除了有视乳头水肿、第六脑神经麻痹或搏动性耳鸣的患者，以排除临床上可能怀疑特发性颅内高压的患者。利拉鲁肽每日给药1.2 mg。该研究于2024年1月至7月进行，随访期为12周。本研究的主要结局是与基线相比，利拉鲁肽治疗12周后每月头痛天数的减少。
我们纳入了31例患者（26例女性，5例男性，平均[标准差，SD]年龄为44.9 [14.6]岁）。治疗后每月平均（SD）头痛天数从19.8（6.7）天降至10.7（7.7）天。这一变化具有显著性，平均差异为9.1天（95%置信区间[CI] 5.41 - 12.84，p < 0.001，Cohen's d：0.90）。相反，BMI从平均（SD）34.0（2.3）kg/m²略有下降至33.9（2.3）kg/m²，且这一变化不具有显著性（平均差异 = 0.1 kg/m²，95% CI -0.004至0.153 kg/m²，p = 0.060，Cohen's d：0.34）。协方差分析表明年龄、性别和伴随用药对头痛频率降低没有显著影响（所有p > 0.050）。简单线性回归分析表明BMI降低对头痛频率降低没有显著预测作用（β = -1.448，95% CI -19.390至16.495，p = 0.870，R = 0.001），表明这两个变量之间没有有意义的关系。
我们的研究结果表明，利拉鲁肽可能对肥胖患者难治性高频或慢性偏头痛有效，且这种效果与体重减轻无关。尽管需要进一步研究来阐明这一主题，但这些发现提出了一个假设，即ICP控制紊乱可能在偏头痛发病机制中起作用，并可能代表一个新的治疗靶点。
