Atogepant, Migraine, and Weight Loss: How Are They Connected?

Atogepant 60 mg once-daily results in clinically meaningful weight loss in individuals with overweight or obesity receiving preventive treatment for migraine, with approximately one-third of individuals experiencing at least a 5% weight reduction. These study results were presented at the 2025 American Headache Society (AHS) Annual Scientific Meeting, held from June 19-22, in Minneapolis, Minnesota, and virtually.

Previous trials have showed the effect of atogepant — approved for the preventive treatment of episodic and chronic migraine — on weight loss in patients with migraine.

Researchers conducted a post hoc analysis to study the association between atogepant use and weight loss in patients with overweight or obesity receiving treatment for episodic and chronic migraine.

Participants for the analysis were enrolled from an ongoing multicenter, open-label, 156-week long-term safety extension study (ClinicalTrials.gov Identifier: NCT04686136) and who completed the ELEVATE or PROGRESS trials (ClinicalTrials.gov Identifiers: NCT04740827 and NCT03855137, respectively).

The researchers collected from the 1-year interim analysis of the open-label study. The safety population included all participants who received at least 1 dose of atogepant in the extension study.

The subgroup population for the analysis was individuals with overweight (body mass index [BMI], ≤25 to <30) or obesity (BMI, ≥30) enriched for cardiovascular risk factors.

Outcomes included change in mean weight over a period of 52 weeks; percentage of participants with a weight decrease of at least 5% or 10% or greater at week 52; and occurrence of weight-related treatment-emergent adverse events (TEAEs).

Of the 595 participants in the open-label safety population, 279 (46.9%) met the study criteria and were included in the post hoc analysis.

Most of the eligible participants were women (83.2%) and White (87.1%). Mean age of the selected cohort was 42.8 years; mean weight was 85.6 kg (188.7 lb); mean BMI was 30.3; and mean monthly migraine days were 14.6. The most common cardiovascular risk factors were hypertension (54.8%) and dyslipidemia (10.4%), in addition to elevated BMI, and approximately 65% of participants had 2 or more cardiovascular risk factors.

At week 4, researchers noted a meaningful weight reduction of 0.95 kg (2.09 lb), with a greater reduction of 3.44 kg (7.58 lb) at 52 weeks. A total of 34.9% and 12.8% of participants had a weight reduction of at least 5% and 10% or more from baseline, respectively. Mean weight loss for the group with at least 5% and 10% weight reduction was 10.0 kg (22.0 lb) and 16.4 kg (36.1 lb), respectively.

In terms of safety, weight-related TEAEs occurred in 1.8% of participants, with 0.4% reporting abnormal weight loss and 0.4% abnormal weight gain. However, these adverse events were not serious and did not lead to study discontinuation.

Overall, the researchers concluded, “In a migraine trial subpopulation enriched for cardiovascular risk factors, clinical meaningful weight loss was observed with atogepant 60 mg once daily throughout the first year of open-label treatment.”

Multiple authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.