What is new in the landscape of insulin-sensitizing agents for polycystic ovary syndrome treatment

Abstract

Polycystic ovary syndrome, the most common gynecological endocrinopathy, is burdened with a state of hyperinsulinemia and insulin resistance in 50–80% of affected women. Wherever the origin of these metabolic abnormalities lies, their pathogenetic role in determining, perpetuating, and worsening the clinical traits of the syndrome is ascertained. Many studies have already highlighted possible mechanisms: hyperinsulinemia and insulin resistance may contribute to hyperandrogenemia, chronic anovulation, and other comorbidities of the syndrome by differentially affecting the endocrine glands (ovaries, adrenals, and pituitary) and peripheral tissues (fat mass and skeletal muscle). Based on these evidences, in the past years, thorough research has been focused on the possible role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Many compounds were tested to verify their efficacy against polycystic ovary syndrome–related metabolic dysfunction, both relying on previous acquired experiences in the field of diabetes mellitus and experimenting new agents, in particular, those belonging to the class of nutraceuticals. We sought to summarize the most relevant aspects of insulin-sensitizing treatments in polycystic ovary syndrome, by reporting the relevant literature on this topic and by keeping an attentive eye on the newly published international guidelines on polycystic ovary syndrome 2018. This overview encompasses metformin, thiazolidinediones, inositols, alpha-lipoic acid, and GLP1-R analogues. Starting from the analysis of the mechanisms of action, we anchored to the state of the art of the use of these drugs in polycystic ovary syndrome, to the most recent evidences for clinical practice and to the remaining open questions around indications, dose, treatment schedules, and side effects.

Efficacy of canagliflozin versus metformin in women with polycystic ovary syndrome: A randomized, open‐label, noninferiority trial

“…Growing evidence indicates that PCOS patients generally have IR and that insulin sensitizers play an important role in the treatment of PCOS. 20,21 SGLT inhibitors, a new class of antidiabetic drug, could ameliorate IR and improve insulin sensitivity in T2DM patients. 11,22 However, limited data are available on the efficacy of SGLT2 inhibitors in the treatment of PCOS patients with IR.…”

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

“…The agonists of glucagon-like peptide-1 (GLP-1) receptor and the inhibitors of dipeptidyl peptidase-4 are widely used to treat T2DM and MetS [ 158 , 159 , 160 , 161 ], but they can also be used to correct the metabolic alterations and IR in PCOS women, as well as in pregnant women with GDM and T2DM [ 162 , 163 ]. It is shown that MF enhances the beneficial effect of liraglutide, a selective GLP-1 receptor agonist, on insulin sensitivity and glucose homeostasis.…”

The Current and Potential Therapeutic Use of Metformin—The Good Old Drug

“…T2DM is a complex disease associated with an increasing risk of some pathological conditions, including obesity, metabolic syndrome, atherosclerotic cardiovascular diseases, certain types of cancer, non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases, PCOS, dementia and metabolic complications of non-retroviral infection [ 5 , 37 , 38 , 39 , 40 , 41 , 42 ]. Growing evidence suggests that metformin may substantially inhibit or delay their progression and improve prognosis, when added to the standard therapy of all of the above-mentioned diseases [ 36 , 41 , 94 , 97 , 98 , 99 , 100 , 101 , 102 ]. Moreover, metformin is sometimes used as an adjunct agent, together with insulin, to treat patients with type 1 diabetes [ 103 , 104 ].…”