From:  Treating obesity with GLP-1 RAs: does sex matter? A commentary on the meta-analysis by Yang et al. (J Diabetes 2025;17(3):e70063)

 Putative mechanisms underlying higher weight loss in women [21–25].

Putative mechanismDirection of the expected sex differenceRef.
PharmacokineticsDifferences in body weight, body composition, and drug clearance are expected to result in higher GLP-1 RA drug bioavailability in women at the same nominal dose. This sex difference would result in greater body weight reduction in females than in males.[21]
HormonalEstrogen and GLP-1 RAs may synergistically activate the supramammillary nucleus, altering food-reward behavior via pro-opiomelanocortin neurons and leading to greater weight loss in females.[22]
Adipose tissue biologyCombining GLP-1 RAs with estrogen may improve leptin resistance, C-reactive protein, and TNF-α, which may contribute to the more substantial weight reduction in females than in males.[22, 23]
Adverse event profileA higher GLP-1 RA incidence of gastrointestinal adverse reactions in females compared to males could contribute to reduced energy intake.[24]
Adherence/behavioral factorsOwing to socio-cultural reasons, women exhibit more stringent adherence to GLP-1 RAs than men.[25]
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GLP-1 RA: glucagon-like peptide-1 receptor agonist.