Liraglutide and polycystic ovary syndrome: is it only a matter of body weight?

Despite Polycystic Ovary Syndrome (PCOS) is a very prevalent disorder among women of reproductive age, there is widespread agreement that until now, no pharmacological options are available to tackle the entire spectrum of clinical manifestations encountered in the clinical practice. Obesity and insulin resistance, which commonly characterized this syndrome, prompted the design of studies investigating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) in PCOS. Indeed, a very impressive number of randomized controlled clinical trials (RCTs) and systematic reviews provided robust evidence on the effectiveness of GLP-1RA in PCOS as a new, appealing approach, producing both satisfactory and permanent weight loss, and improvement of insulin resistance at the same time. However, most of the subjects included in the RCTs are PCOS patients with obesity/overweight, whereas a portion of PCOS women, which can even reach 50%, might present a lean phenotype. Moreover, some benefits on clinical and metabolic features of PCOS may not have fully emerged due to the low or medium doses employed in the vast majority of the current studies. Thus, pitfalls in the methodology of these studies have led sometimes to misleading results. In addition, some aspects of GLP-1 beyond weight loss, such as preclinical evidence on GLP-1 effects in directly modulating the hypothalamus–pituitary–gonadal axis, or the effects of GLP-1RA on clinical and biochemical expression of hyperandrogenism, still deserve a greater insight, especially in light of a possible therapeutic use in PCOS women independently of obesity. Aim of this review is to further unravel the possible role of GLP-1 in PCOS pathogenesis, tempting to provide additional supports to the rationale of treatment with GLP-1RA in the management of PCOS also independent of weight loss. For this purpose, the outcomes of RCTs investigating in PCOS the anthropometric and metabolic changes have been treated separately to better underpin the effects of GLP-1 RA, in particular liraglutide, beyond weight loss.