Obesity and its treatment: Toward new approaches

Abstract

Obesity has until now been defined in terms of body mass index, a parameter which lacks sensitivity. The definition rather needs to take account of the pathophysiology and impact of the mechanical, metabolic and psychological complications associated with excess adiposity, as proposed by the French Health Authority in 2022. Initial phenotyping of pathophysiological determinants and complications make it possible to precisely define treatment objectives and the means used to achieve them. For example, excess adiposity is associated with hypervolemia, which increases the risk of heart failure independently of classic cardiovascular risk factors, due in particular to myocardial remodeling and diastolic dysfunction. In this indication, SGLT2 (sodium/glucose cotransporter 2) inhibitors may be relevant. A global approach, involving assessment of eating behavior and sensations, energy expenditure and emotional eating, enables us to identify drug treatments suited to each profile. Obesity is a recurrent pathology requiring the development of new combined or sequential drug treatments. Currently under development, inhibitors of the myostatin/activin A pathway conserve lean body mass during weight loss, a crucial factor in limiting weight regain and maintaining functional capacity. Beyond medical or surgical approaches to obesity, lifelong lifestyle interventions are central to improving quality of life and limiting the risks associated with excess adiposity.