Atogepant 60 mg daily induces significant weight loss in long-term migraine treatment
Background
The comorbidity between obesity and migraine, particularly chronic migraine (CM), is well-established, with individuals with obesity facing a higher risk and burden of migraine. The calcitonin gene-related peptide (CGRP) pathway, a key player in migraine pathophysiology, has also been implicated in metabolic regulation and obesity. While atogepant, a CGRP receptor antagonist approved for migraine prevention, has shown incidental weight loss in shorter 12-week and 40-52-week trials for episodic migraine (EM), its long-term impact on body weight in patients with higher migraine burden (EM or CM) had not been thoroughly investigated. This study addresses that gap by evaluating weight changes over an extended period.
Study Design
This interim analysis, part of study 312 (a phase 3, open-label, 156-week extension study), assessed weight loss in participants with chronic migraine (CM) or episodic migraine (EM) who had previously failed two to four conventional oral preventive medications. Participants from prior PROGRESS (CM) and ELEVATE (EM) lead-in studies rolled over into study 312, receiving atogepant 60 mg once daily. The primary safety endpoint was the change from baseline in body weight at each visit through the end of treatment or up to week 52. Researchers also evaluated the proportion of participants achieving ≥5% weight loss at any time, at the end of the lead-in study, or at week 52 in study 312.
Results
A total of 595 participants from the PROGRESS (n=325) and ELEVATE (n=270) studies were enrolled in study 312, all treated with atogepant 60 mg once daily.
Mean body weight significantly decreased over time, with a mean reduction of -2.16 kg (standard deviation 5.89 kg, equivalent to -4.76 lb) observed at week 52 of treatment. This weight reduction was clinically meaningful for a substantial portion of the cohort: 44.8% (265/592) of participants experienced a ≥5% weight loss at any point during the study. Furthermore, 29.5% (140/474) of participants achieved a ≥5% weight loss specifically at the week 52 mark. These findings suggest a sustained effect of atogepant on body weight over the long term in this migraine population.
Key Findings
- Atogepant 60 mg daily led to a mean body weight decrease of -2.16 kg at week 52.
- 44.8% of participants experienced ≥5% weight loss at any time during the study.
- 29.5% of participants achieved ≥5% weight loss specifically at week 52.
- The study included 595 participants with chronic or episodic migraine.
Why It Matters
This study highlights a significant and sustained weight loss effect of atogepant in patients with high-burden migraine, a population often struggling with comorbid obesity. For clinicians and patients, this offers a potential dual benefit: effective migraine prevention coupled with a favorable impact on body weight, which is particularly valuable given that many migraine preventives can cause weight gain. Atogepant could become a preferred therapeutic option for migraineurs who are overweight or obese, simplifying treatment regimens and improving overall health outcomes. While this was an open-label extension, the consistent weight reduction observed over 52 weeks suggests a robust effect, moving us closer to understanding the full metabolic profile of CGRP receptor antagonists and potentially informing future treatment guidelines for migraine management.
atogepant
migraine
weight loss
cgrp antagonist
obesity
phase 3