sitagliptin-phosphate and Polycystic-Ovary-Syndrome

To evaluate the effects of sitagliptin on the metabolic indices and hormone levels in patients with polycystic ovary syndrome (PCOS). PubMed, EMBASE, Web of Science, Cochrane Library, WanFang Data, and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) published up to March 2022. Eligible studies were identified based on the inclusion criteria. The primary outcomes included the homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone level (TT). Other outcomes included levels of sex hormones, glucose, and lipid metabolism. Forty-five studies were initially identified, and 6 RCTs with 394 patients were finally included in this study. The meta-analysis results suggest that sitagliptin improved HOMA-IR (WMD =  - 0.35; 95% CI (- 0.62, - 0.08); P = 0.01), BMI (WMD =  - 1.27; 95% CI (- 1.76, - 0.77); P < 0.00001), TT (SMD =  - 0.66; 95% CI (- 1.25, - 0.07); P = 0.03), and HDL-C (SMD = 0.11; 95% CI (0.03, 0.18); P = 0.005). No significant differences were observed between the sitagliptin and control groups in other outcomes and in terms of adverse events. Evidence from meta-analyses suggests that sitagliptin was superior in improving insulin sensitivity, total serum testosterone, high-density lipoprotein, and body mass index. However, due to the limitations of published studies, it is difficult to draw a definite conclusion. Larger, higher-quality studies are needed to evaluate the efficacy of sitagliptin in women with PCOS.

Topics: Female; Humans; Insulin Resistance; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Testosterone

The aim of this study was to investigate the effects of sitagliptin/metformin (sitaformin), metformin and sitagliptin in PCOS patients. PCOS is a hormonal disorder and therefore the use of treatments that modulate hormone levels Like AMH, testosterone, insulin, leptin and especially FAI and HOMA-IR can reclaim the symptoms of PCOS. PCOS also increases oxidative stress and lipid peroxidation. Therefore, in clinical and research trials, the level of these factors is usually examined to reduce patients' symptoms. Participants were randomly assigned to receive metformin, sitagliptin, sitaformin or placebo Treatment was carried out 2 months before the start of the ovulation cycle and continued until the day of ovum pick up. The serum levels of HOMA-IR and FAI decreased significantly in the treated groups compared to the placebo. The serum and the FF levels of leptin also decreased significantly in the sitaformin group when compared to the metformin and sitagliptin groups. Moreover, the serum and FF levels of AMH and MDA had a significant decrease in the sitaformin and sitagliptin group compared to the placebo. The mRNA expression and protein levels of GDF9 and BMP15 in the cumulus cells increased significantly in the sitaformin compared to metformin and sitagliptin groups. The expression level of GDF9 and BMP15 mRNA were positively correlated with the fertilization rate and grade I embryos. Sitaformin improves levels of GDF9 and BMP15 in PCOS compared to metformin and sitagliptin, which can increase the rate of fertilization and grade I embryos.

Topics: Bone Morphogenetic Protein 15; Female; Fertilization; Growth Differentiation Factor 9; Humans; Leptin; Metformin; Polycystic Ovary Syndrome; RNA, Messenger; Sitagliptin Phosphate

Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired vascular function. GH-releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion.. We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS.. Eighteen women with PCOS participated in a double-blind, crossover study. They received sitagliptin either 100 mg or placebo daily for 1 month, with crossover treatments separated by an 8-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT) and assessments of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm.. During OGTT, sitagliptin increased glucagon-like peptide-1 (P < 0.001), early insulin secretion (from mean [± SD] insulinogenic index 1.9 ± 1.2 to 3.2 ± 3.1; P = 0.02), and decreased peak glucose (mean -17.2 mg/dL [95% CI, -27.7 to -6.6]; P < 0.01). At 1 month, sitagliptin decreased VAT (from 1141.9 ± 700.7 to 1055.1 ± 710.1 g; P = 0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9 ± 3.6 to 17.0 ± 6.8 min, N = 16; P = 0.04) and interpulse interval (from 53.2 ± 20.0 to 77.3 ± 38.2 min, N = 16; P < 0.05) but did not increase mean overnight GH (P = 0.92 vs placebo).. Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval.. This study was registered at www.clinicaltrials.gov as NCT02122380 prior to enrollment of the first participant.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Cross-Over Studies; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Follow-Up Studies; Glucose Tolerance Test; Human Growth Hormone; Humans; Intra-Abdominal Fat; Middle Aged; Polycystic Ovary Syndrome; Prognosis; Sitagliptin Phosphate; Young Adult

Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated the dipeptidyl peptidase 4 inhibitor sitagliptin as a potential treatment option in metformin-intolerant PCOS.. We conducted a 12-week, prospective, randomized, open-label study with 30 obese metformin-intolerant women with PCOS (age 35.0 ± 7.2 years; body mass index, 36.9 ± 5.5 kg/m. SITA improved beta-cell function as assessed by the homeostasis model assessment for beta-cell function index (HOMA-B) of 45.9 ± 35.8 ( P = .001), modified beta-cell function index (MBCI) of 7.9 ± 7 ( P = .002), and quantitative insulin-sensitivity check index (QUICKI) of -0.03 ± 0.03 ( P = .002). By contrast, beta-cell function decreased in CON. The between-group differences were significant for HOMA-B ( P = 0.001), MBCI ( P = .010), and QUICKI ( P = .025). The conversion rate to impaired glucose homeostasis was prevented in SITA: 3 of 15 subjects had impaired glucose tolerance (IGT) before and after the study. In CON, none had type 2 diabetes (T2D), and 4 had IGT at the beginning. After 12 weeks, IGT was observed in 2 and T2D in 3 subjects.. SITA improved beta-cell function and prevented a conversion to IGT and T2D in metformin-intolerant obese PCOS patients.. BMI = body mass index; DPP-4 = dipeptidyl peptidase-4; DXA = dual energy X-ray absorptiometry; GIP = glucose-dependent insulinotropic peptide; GLP-1 = glucagon-like peptide-1; HOMA-B = homeostasis model assessment for beta-cell function; HOMA-IR = homeostasis model assessment of insulin resistance; IAI = insulin action index; IGT = impaired glucose tolerance; IR = insulin resistance; MBCI = modified beta-cell function index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index; PCOS = polycystic ovary syndrome; SHBG = sex hormone-binding globulin; T2D = type 2 diabetes.

Topics: Absorptiometry, Photon; Adult; Body Composition; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Disease Progression; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Secreting Cells; Life Style; Obesity; Pilot Projects; Polycystic Ovary Syndrome; Sitagliptin Phosphate

Dipeptidyl peptidase 4 (DPP4) has been revealed to be upregulated in women suffering from polycystic ovary syndrome (PCOS), which is a common reproductive disorder. The present study was designed to investigate the effects of inhibition of DPP4 expression on the proliferation of ovarian granulosa cells as well as on the activation of the cAMP response element‑binding protein (CREB)/aromatase pathway. The expression levels of DPP4 in rat serum samples with or without PCOS and ovarian granulosa cells (KGN cells) were detected using reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analyses. Cell viability and cell cycle progression were detected using the Cell Counting Kit‑8 assay and flow cytometric analysis, respectively. The 5‑ethynyl‑2'‑deoxyuridine assay was employed to detect the proliferation of glycolaldehyde‑bovine serum albumin (GOA‑BSA)‑treated KGN cells. In addition, RT‑qPCR and western blot analyses were applied to detect the expression levels of CREB, specific cell cycle‑associated proteins and cytochrome P450 (CYP) 19A1 and CYP11A1 enzymes in KGN cells. The expression levels of DPP4 were upregulated in rats with PCOS. Inhibition of DPP4 expression promoted the proliferation and cell cycle arrest of KGN cells. It was also revealed that the expression levels of cell cycle‑associated proteins were upregulated in DPP4‑silenced KGN cells. In addition, their proliferation was decreased following treatment with GOA‑BSA, while the addition of sitagliptin partially reversed these effects. Additionally, sitagliptin reversed the inhibitory effects caused by GOA‑BSA treatment on the cell cycle progression and on the activation of the CREB/aromatase pathway in KGN cells, as determined by the increased expression levels of the cell cycle‑associated proteins as well as those of the CREB protein and the CYP19A1 and CYP11A1 enzymes. In conclusion, inhibition of DPP4 expression promoted the proliferation of KGN cells and the activation of the CREB/aromatase pathway.

Topics: Animals; Aromatase; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cholesterol Side-Chain Cleavage Enzyme; Cyclic AMP Response Element-Binding Protein; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Female; Granulosa Cells; Humans; Polycystic Ovary Syndrome; Rats, Sprague-Dawley; Serum Albumin, Bovine; Signal Transduction; Sitagliptin Phosphate; Up-Regulation

Insulin resistance plays a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, there is a growing interest in the use of insulin sensitizer drugs in the treatment of PCOS. Research in recent years has shown that sitagliptin has been reported to improve ovarian cycles and ovulation in PCOS patients.. We aimed to compare the effects of metformin and sitagliptin on PCOS individuals undergoing ICSI.. Sixty PCOS patients were divided into 3 groups: metformin, sitagliptin, and placebo group. Treatment was carried out 2 months before the start of the ovulation cycle and continued until the day of oocyte aspiration. The serum levels of total testosterone, estradiol, and fasting insulin along with the total number of retrieved, normal and abnormal MII, and fertilized oocytes, the number of transferred embryos (grades I, II and III), and biochemical and clinical pregnancy rates as well as the ovarian hyperstimulation syndrome (OHSS) were evaluated.. There was a significant reduction in the serum levels of Insulin and total testosterone in the treated groups compared with the placebo. The number of mature and normal MII oocytes increased significantly in the treated groups compared with the placebo. Moreover, the number of immature oocytes decreased significantly and the number of grade I embryos increases significantly in the sitagliptin group compared with the placebo group.. We conclude that sitagliptin can improve the maturation of oocytes and embryos' quality more effectively than metformin, in PCOS patients undergoing ICSI.. Trial registration is NCT04268563 ( https://clinicaltrials.gov ).

Topics: Adult; Female; Humans; Metformin; Oocytes; Polycystic Ovary Syndrome; Sitagliptin Phosphate; Sperm Injections, Intracytoplasmic

Metformin has long been used in the treatment of polycystic ovarian syndrome (PCOS). Recently, sitagliptin has been reported to improve ovarian cycles and ovulation in PCOS. We suggest that a combination of sitagliptin and metformin can be more effective than either treatment alone in improving different aspects of PCOS.

Topics: Female; Humans; Menstrual Cycle; Metformin; Ovulation; Polycystic Ovary Syndrome; Sitagliptin Phosphate

Insulin resistance (IR) is prevalent in women with polycystic ovary syndrome (PCOS). Improvement in insulin sensitivity remains one of the most effective treatment strategies for women with PCOS. This study aims to investigate the efficacy and potential mechanism of the combination therapy with metformin (DMBG) and sitagliptin (TECOS) in PCOS. To address this, insulin was used to treat rat ovarian granulosa cells to establish the cellular PCOS model. Insulin and human chorionic gonadotropin (HCG) were subcutaneously injected into SD rats to establish a rat model of hyperandrogenism with pathogenesis similar to PCOS. Our results showed that co-treatment with TECOS and DMBG attenuated the induced apoptosis and insulin resistance (IR) in PCOS model cells, and improved reproductive hormone disorders, ovarian polycystic changes, and IR of PCOS rats. Mechanistically, upregulation of H19 by H19-expressing lentiviruses enhanced efficacy of combination therapy. Furthermore, co-treatment with TECOS and DMBG induced H19 expression via suppressing the PI3K/AKT-DNMT1 pathway. Collectively, these findings demonstrate that combination treatment with TECOS and DMBG ameliorates PCOS with IR, at least partially, through upregulation of lncRNA H19.

Topics: Animals; Apoptosis; Cells, Cultured; DNA (Cytosine-5-)-Methyltransferase 1; Drug Therapy, Combination; Female; Gonadal Steroid Hormones; Granulosa Cells; Insulin; Insulin Resistance; Luteinizing Hormone; Metformin; Phosphatidylinositol 3-Kinases; Phosphorylation; Polycystic Ovary Syndrome; Progesterone; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; RNA, Long Noncoding; Sitagliptin Phosphate

Examine the effects of dipeptidyl peptidase-4 (DPP4) inhibitor Sitagliptin on the transforming growth factor-β1 (TGF-β1) signal transduction pathway in polycystic ovary syndrome (PCOS) rats with ovarian fibrosis.. Thirty rats were divided randomly into the PCOS model group, Sitagliptin treatment group and blank control group. Dehydroepiandrosterone was administered to the model group and treatment group to establish the models. Then, the phenotype of rats was recorded, and the serum sex hormone levels were measured. The pathological structures of the rat ovaries were observed. The protein and mRNA expression levels of DPP4, connective tissue growth factor (CTGF), TGF-β1 and Smad2/3 in the ovaries were analyzed.. There was no statistically difference in fasting body weight and blood glucose among the three groups before Sitagliptin treatment (P > 0.05). The fasting blood glucose level was significantly decreased after the administration of Sitagliptin (P < 0.05). The level of testosterone in the model group was reduced remarkably after Sitagliptin treatment (P < 0.001). The protein expression levels of DPP4, CTGF and TGF-β1 in the ovarian stroma were lower in the treatment group than in the model group (P < 0.01, P < 0.001, P < 0.05). The mRNA levels of DPP4, CTGF and TGF-β1 in the model group also greatly declined after Sitagliptin treatment (P < 0.05, P < 0.001, P < 0.01).. The DPP4 inhibitor Sitagliptin lowers fasting blood glucose, relieves the high androgen state of PCOS rats and delays the process of ovarian fibrosis, which may be related to reducing the levels of factors related to the TGF-β1/Smad2/3 signaling pathway.

Topics: Animals; Blood Glucose; Dipeptidyl-Peptidase IV Inhibitors; Female; Fibrosis; Ovary; Polycystic Ovary Syndrome; Rats; Signal Transduction; Sitagliptin Phosphate; Transforming Growth Factor beta1