**1. Introduction**

Obesity is one of a key phenotype of polycystic ovary syndrome (PCOS). The risk for excess body weight in this population is up to 2.8 higher than in women without PCOS. About 60–70% of patients are being characterized as obese or overweight [1, 2]. The amount and distribution of fat is a major contributor to expression and severity of the syndrome [3, 4]. Obese women demonstrate more severe gynecological abnormalities and clinical and biochemical hyperandrogenism than normal weight or lean women with PCOS. Insulin resistance, glucose derangements including impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) and an increased overall cardiovascular risk are also more likely in obese PCOS [5–7]. Weight reduction is substantial for improvement of metabolic and androgen profile, reproductive function and reducing cardiovascular risk. Weight management by lifestyle intervention often remains unsatisfactory and nonsustainable. In the present chapter, we revised limited studies addressing the potential use of agents mediating through glucagon-like peptide 1 (GLP-1) in obese PCOS. We mainly focused on the available clinical trials of GLP-1 receptor agonists in this population. In addition, we challenged the original concept related to the enhancement of GLP-1–mediated action through phosphodiesterase 4 (PDE4). Nevertheless, we considered dipeptidyl peptidase 4 inhibitors as an alternative pharmacological intervention in subgroups of PCOS with high metabolic risk.

of PCOS, suggesting that androgens have appetite-stimulating effects and could impair the impulse control of eating behavior [15]. Disturbed appetite was also associated with altered opioid function demonstrated in PCOS linked to the stimulation of food intake and appetite for high fat/high glucose food through hedonistic centers in hypothalamus [16]. In addition, there are some evidences that disturbed regulation of gastrointestinal signals, in particular

Incretin System: New Pharmacological Target in Obese Women with Polycystic Ovary Syndrome

http://dx.doi.org/10.5772/intechopen.70648

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Incretins are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). They are polypeptide gut hormones secreted from endocrine cells in the small intestine under the influence of food intake and are responsible for 50–70% of postprandial insulin secretion. This is so-called incretin effect and is proportional to the current glycemia [8, 22].

GLP-1 is produced by L cells in distal intestine. It influences glucose hemostasis after food ingestion by insulin secretion and concurrent inhibition of glucagon release. GLP-1 is involved in the regulatory mechanisms of eating behavior with direct inhibitory effect on the homeostatic and hedonic centers of appetite in the central nervous system and indirect inhibitory effect on gastric emptying rates and gastrointestinal tract motility, which result in decreased

GIP is produced by K cells, which are located in the upper small intestine. It increases glucosedependent insulin release and has protective effect on beta cell. GIP also increases lipogenesis and has bone protective and neuroprotective effect. In contrast to GLP1, no additional effects

Both incretin hormones have a short half-life. They are rapidly inactivated by the enzyme

Obesity with the onset of insulin resistance and consequent metabolic diseases, such as impaired glucose tolerance and type 2 diabetes, impairs the effect of incretins. Postprandial GLP-1 concentration in obese people is lower than in people with normal body weight [24–27]. Similarly, lower postprandial GLP-1 values were measured in patients with type 2 diabetes,

Current reports about GLP-1 secretion in PCOS are not consistent. Some studies found similar fasting GLP-1 levels in PCOS compared with age- and BMI-matched controls [21, 33–35], whereas others reported decreased or increased fasting levels of GLP-1 in PCOS [36, 37]. Regarding postprandial levels of GLP-1, some authors demonstrated that postprandial plasma levels of GLP-1 did not differ between subjects with and without PCOS [20, 34, 35]. On the other hand, another study demonstrated lower GLP-1 levels in PCOS at the end of oral glucose tolerance test (OGTT) compared to the control group, whereas fasting GLP-1 levels did not differ between two groups [21]. However, lower fasting GLP-1 levels and a weakened GLP-1 response to standardized mixed meal in women with PCOS versus healthy control

food intake and consequently in body weight reduction [8, 23].

while the GIP response in this population was preserved [28–32].

on appetite and body weight are shown with GIP [22].

dipeptidyl peptidase 4 (DPP4).

**2.3. Incretin hormones in PCOS**

incretins, are intrinsic to PCOS [15, 17–21].

**2.2. Incretin hormones**
