Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences. A plethora of symptoms and their severity differentiate on an individual level, giving the syndrome numerous phenotypes. Due to menstrual cycle abnormalities, women suffer from irregular menstrual bleeding, difficulty in conception, and infertility. Furthermore, the risk of pregnancy complications such as gestational diabetes mellitus, hypertensive disorders of pregnancy, and preterm birth are higher in women with PCOS than in the general population. Often, women with PCOS have comorbidities such as dyslipidemia, obesity, glucose intolerance or diabetes type 2, non-alcoholic fatty liver disease, and metabolic syndrome, which all influence the treatment plan. Historic insulin-sensitizing agents, although good for some of the metabolic derangements, do not offer long-term cardiovascular benefits; therefore, new treatment options are of paramount importance. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, a new class of antidiabetic agents with beneficial cardiovascular, bodyweight, and antihyperglycemic effects, although not approved for the treatment of PCOS, might be an attractive therapeutic addition in the PCOS armamentarium. Namely, recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with PCOS. It is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic, reproductive, and psychological consequences.

SGLT-2 inhibitors in obesity and its associated cardiometabolic disorders: where do we stand?

“…The latter feature is responsible for the metabolic derangement related to PCOS and the increased CVD risk. In this case, insulin sensitizers, such as metformin or thiazolidinediones may be alternative drugs instead of oral contraceptives [83]. As approximately 60% to 70% of women with PCOS will, at last, develop insulin resistance and hyperinsulinemia.…”

The role of Sirtuin 1 in the pathophysiology of polycystic ovary syndrome

“…Lira has been shown to induce the expression of adenosine monophosphate activated protein kinase-α (AMPK-α) and SIRT-1 proteins and promote brown adipocyte differentiation and anti-inflammatory effects, thereby improving insulin sensitivity, reducing inflammation, and inducing adaptive thermogenesis [ 105 ]. In addition, sodium–glucose cotransporter 2 (SGLT-2) inhibitors, such as licogliflozin increase insulin sensitivity and ameliorate hyperinsulinemia and hyperandrogenemia in women with PCOS [ 106 – 108 ]. Unfortunately, there is currently a lack of studies on the interaction between SGLT2 inhibitors and SIRT1, which is also a new direction for future research.…”

Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: A single-center, open-labeled prospective randomized controlled trial

“…Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, novel hypoglycemic oral drugs that promote renal glucose loss ( 27 ), are widely used clinically in patients with diabetes. Many studies have shown that SGLT-2 inhibitors can reduce fat mass ( 28 ), and blood pressure ( 28 ), ameliorate glucose homeostasis ( 29 ), alleviate oxidative damage and inflammation ( 30 ), and protect the cardiovascular system ( 31 ).…”

“…In addition, several studies have substantiated the view that SGLT-2 inhibitors can significantly reduce weight in non-diabetic overweight and obese individuals with few adverse events (AEs) ( 32 – 36 ). Based on the advantages of both anthropometric and metabolic profiles, the emergence of SGLT-2 inhibitors for PCOS treatment has aroused general interest ( 27 , 37 ). Cai et al.…”