Obesity, incretin-based therapies, and cardiovascular disease in women

Abstract Obesity in women is a growing and multifaceted public health challenge, driven by complex interactions among biological, hormonal, and psychosocial factors across the life course. From menarche to menopause, hormonal fluctuations influence fat distribution, energy balance, and metabolic risk, contributing to sex-specific trajectories of weight gain. Moreover, women-specific conditions, such as pregnancy-related weight retention, hypertensive disorders of pregnancy, and polyendocrine metabolic ovarian syndrome, further amplify long-term cardiometabolic risk. Women with obesity have an increased risk of heart failure with preserved ejection fraction and ischemia with non-obstructive coronary arteries. Emerging pharmacological treatments for obesity, including incretin-based therapies, offer an evidence-based addition to lifestyle interventions and metabolic and bariatric surgery and have demonstrated substantial weight loss effects and cardiovascular benefits. However, sex-specific differences in efficacy, tolerability, and long-term outcomes of these new pharmacological treatments remain insufficiently researched. Moreover, concerns regarding reproductive health and access to care uniquely affect women. This review addresses the need for a life course and sex-specific approach to obesity and its treatment, integrating metabolic, reproductive, and cardiovascular perspectives.