Effect of metformin versus metformin plus liraglutide on gonadal and metabolic profiles in overweight patients with polycystic ovary syndrome

Abstract

ObjectiveTo observe the effect of metformin (MET) monotherapy versus MET plus liraglutide (LIRA) on gonadal and metabolic profiles in overweight patients with polycystic ovary syndrome (PCOS).MethodsSixty overweight patients with PCOS were recruited from January 2021 to January 2022 in Shengjing Hospital of China Medical University and were randomly assigned to the MET or combination (COM) group to receive 12 weeks of MET monotherapy or MET plus LIRA therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and oral glucose tolerance tests (OGTT) were conducted at baseline and after the 12-week treatment.ResultsFifty-two subjects completed the trial while eight were lost during the follow-up. Both MET and COM improved menstrual cycles, anthropometric parameters, and glucose metabolism after the 12-week treatment; however, there was no statistical difference between the two groups. MET plus LIRA therapy improved hyperandrogenemia, including TT (total testosterone), SHBG (sex hormone binding globulin) and FAI (free androgen index), whereas MET monotherapy only improved SHBG and FAI when compared with baseline. Furthermore, both MET monotherapy and MET plus LIRA therapy improved E2 (estradiol) while only MET plus LIRA therapy improved LH (luteinizing hormone), FSH (follicle stimulating hormone) and Prog (progesterone) more effectively than baseline. Additionally, MET plus LIRA therapy may improve TT, SHBG, FAI, LH and Prog more effectively than MET monotherapy; however, there were no significant differences on E2, FSH and LH/FSH between the two groups.ConclusionsIn overweight patients with PCOS, both MET monotherapy and MET plus LIRA therapy improved glucose metabolism and relieved insulin resistance (IR). Additionally, MET plus LIRA therapy was more effective than MET monotherapy in improving reproductive abnormalities and hyperandrogenemia, potentially by modulating the hypothalamic-pituitary-ovarian axis.

Short-term effect of beinaglutide combined with metformin versus metformin alone on weight loss and metabolic profiles in obese patients with polycystic ovary syndrome: a pilot randomized trial

“…found that after 24 weeks of therapy with the combination of exenatide and MET, the TT levels also considerably reduced ( 9 ). This result differed from that of Chuan Xing et al ( 29 )and Liu et al ( 40 ), who randomized overweight/obese PCOS patients to receive exenatide or liraglutide combined with MET versus MET alone for 12 weeks and found that neither group saw a clear decrease in the TT levels. There is now widespread agreement that the most sensitive indicator of hyperandrogenaemia is blood concentrations of free testosterone, which exerts biological effects on tissues not by TT ( 41 ), And sex hormone-binding globulin (SHBG) as a marker of IR and metabolic complications in PCOS is widely advocated ( 15 ).…”

“…It seems that weight loss could be beneficial to clinical(reproductive and metabolic) outcomes in PCOS patients ( 26 , 27 ). Although many studies have confirmed the weight reduction effects of metformin and GLP-1RA ( 15 , 28 , 29 ), the potential action of beinaglutide combined with metformin versus metformin alone on weight loss in PCOS has not yet been studied.…”

“…Androgen excess secretion is a prerequisite for PCOS development which arises from dysregulation of the hypothalamus-pituitary-ovary axis(HPOA), leading to sensitize ovarian steroidogenesis in response to enhancement of LH and P450c 17α-hydroxylase hyperactivity of follicular theca cells. Subsequently, elevated levels of androgens account for the maturation arrest of FSH-sensitive follicles and can not grow to normal size, causing ovulatory dysfunction ( 29 ). The observation that an imbalance ratio of LH/FSH is one of the common hormonal changes of HPOA function disorders and LH/FSH>2 may have enhanced the activity of adrenal-derived androgens, worsening hyperandrogenemia symptoms such as hirsutism and acne in PCOS patients ( 4 , 29 ).…”

“…Subsequently, elevated levels of androgens account for the maturation arrest of FSH-sensitive follicles and can not grow to normal size, causing ovulatory dysfunction ( 29 ). The observation that an imbalance ratio of LH/FSH is one of the common hormonal changes of HPOA function disorders and LH/FSH>2 may have enhanced the activity of adrenal-derived androgens, worsening hyperandrogenemia symptoms such as hirsutism and acne in PCOS patients ( 4 , 29 ). Hence, lowering high androgen levels and recovering HPOA normal rhythm are necessary to improve hyperandrogenism symptoms and ovarian dysfunction in obese patients with PCOS.…”

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

“…These effects still deserve a greater insight, especially in the light of a possible therapeutic use in PCOS women independently of obesity. Contrariwise, other relevant aspects, such as the safety profile and tolerability of GLP-1RA or the beneficial effects on fertility in PCOS, have been more extensively treated, especially considering that possible direct or indirect reproductive effects of GLP-1 RA might require a concomitant effective contraception and a washout period before pregnancy [22,[24][25][26][27][28][29][30][31].…”