Sex Differences in Obesity and Its Treatment

Researchers and clinicians have increasingly recognized the importance of investigating and considering sex differences in obesity treatment. In this narrative review, we first summarized sex differences in select obesity-related conditions that have been the focus of studies of second-generation anti-obesity medications (i.e., semaglutide and tirzepatide) including type 2 diabetes, obstructive sleep apnea, knee osteoarthritis, and heart failure. We next described sex differences related to obesity treatments with a focus on the second-generation anti-obesity medications, semaglutide and tirzepatide.

Type 2 diabetes, obstructive sleep apnea, knee osteoarthritis, and heart failure demonstrated sex-specific pathways influenced by factors such as hormones and body composition. Lifestyle modification, on average, resulted in larger weight losses in males. In contrast, second-generation AOMs produced higher mean weight losses among females. Females reported more adverse events (e.g., nausea, vomiting) with second-generation anti-obesity medications. The few studies that have performed analyses of changes in obesity-related comorbidities stratified by sex have shown consistent improvements between males and females in heart failure and cardiovascular outcomes. Studies are needed to evaluate the effect of sex on the efficacy of anti-obesity medications including on mental health, investigate the mechanisms underlying these effects, and develop interventions to improve the availability and access of these medications.