ObjectivesCanagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy’s efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS).MethodsFifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated.ResultsCompared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively.ConclusionsIn overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy.Trial registrationClinicalTrials.gov, NCT04973891.

Objective: This research evaluated the efficacy of oral nutritional agents including CoQ10, vitamin E, inositols and vitamin D on androgen-associated hormones, glycolipid metabolism and body weight in women with PCOS. Method: A multi-database search was performed from inception to December 2020. Using multi-variate random effects method, a NMA was conducted by synthesizing data pooled from RCTs. It was registered with PROSPERO (registration number CRD42021230292). Results: Twenty-three RCTs and 1291 participants were included. Based on NMA, CoQ10, vitamin E, CoQ10 combined with vitamin E, and inositols were successful in decreasing TT as compared with PA; vitamin E was superior to other agents. Vitamin E and inositols were successful in increasing SHBG levels; inositols were stronger than vitamin E. CoQ10 alone or combined with vitamin E, and inositols were successful in decreasing HOMA-IR. Inositols had the best results among included nutraceuticals to ameliorate HOMA-IR, FBG, FINS, TG, TC, and LDL-C and correlated to improvements in BMI. There was no significant difference between the CoQ10 or vitamin E group and the PA group in ameliorating lipid metabolism, and vitamin D had no positive effects in ameliorating hyperandrogenism, BMI, glycolipid metabolism profiles compared with PA. Conclusion: For women with PCOS, inositols supplementation have some certain advantages in increasing SHBG and improving glycolipid metabolism when compared with nutraceuticals like CoQ10, vitamin E, vitamin D. Besides, vitamin E may be a better option in reducing TT and increasing SHBG. CoQ10 alone or combined with vitamin E can be helpful in decreasing HOMA-IR as well.

IntroductionPolycystic ovary syndrome (PCOS) is a heterogeneous reproductive endocrine disorder. Several ongoing trials test sodium-glucose cotransporter-2 (SGLT-2) inhibitors for women with PCOS. However, their effectiveness has not been fully elucidated owing to the lack of high-confidence evidence. Our group agrees with the statement that SGLT-2 inhibition could treat PCOS as it is supported by reports demonstrating the benefits of SGLT-2 inhibition on metabolic status and weight control. Moreover, the functions of chronic inflammation amelioration and cardiovascular system protection make it a more attractive candidate for PCOS therapy. Therefore, to provide physicians with a reference, we intend to perform a meta-analysis on the efficacy and safety of SGLT-2 inhibitors on the endocrine and metabolic profiles of patients with PCOS.Methods and analysisWe will search for randomised controlled trials performed until September 2022 using PubMed, Web of Science, EMBASE, the Cochrane Library, Google Scholar, the PhRMA Clinical Study Results Database (www.clinicaltrials.gov), the China National Knowledge Infrastructure, the Wanfang, the Weipu and the Chinese biomedical literature databases. The outcomes will include androgen-associated outcomes, body fat, glucose and lipid homoeostasis, inflammatory outcomes and adverse events. In addition, two investigators will independently assess methodological quality using the revised Cochrane risk-of-bias tool 2. The analysis will be performed using RevMan V.5.3 software, and subgroup and sensitivity analyses and a meta-regression will be used to determine the heterogeneity source.Ethics and disseminationEthical approval is not required because this is a meta-analysis. We will disseminate these results by publishing them in a peer-reviewed journal.PROSPERO registration numberCRD42021281176.