Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: A single-center, open-labeled prospective randomized controlled trial.
Canagliflozin (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).
Fifty-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.
Compared 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.
In 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.
ClinicalTrials.gov, NCT04973891.
Zhang J
，Xing C
，Cheng X
，He B
... -
《Frontiers in Endocrinology》
A Meta-Analysis of the Effect of Sodium Glucose Cotransporter-2 Inhibitors on Metabolic Parameters in Patients With Polycystic Ovary Syndrome.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of childbearing age and is associated with multiple morbidities. However, treatment for this condition is mainly applied for symptomatic relief and does not address the complex pathophysiology of this condition. This meta-analysis was conducted on the usage of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in PCOS because this group of drugs presents an attractive strategy to address the metabolic and hormonal defects by managing the pathophysiological defects observed in this syndrome.
We included prospective trials that enrolled patients with established PCOS and compared an SGLT-2i group versus a control group with at least 2 weeks of follow-up. The standardized mean difference (SMD) was used for effect size estimation from individual studies and was pooled using the fixed effect model.
We included four trials with a pooled population of 158 patients with documented PCOS who received either an SGLT-2i or standard management. From a metabolic perspective, significant improvements were observed in the reduction in body weight (SMD: -0.68, 95% CI -1.16 to -0.19, <0.01), fasting plasma glucose (FPG) (SMD: -0.59, 95% CI -0.99 to -0.19, P<0.01), and insulin resistance as assessed with the HOMA-IR (SMD: -0.39, 95% CI -0.76 to -0.03, P=0.03). In addition, a significant improvement was noted in dehydroepiandrosterone sulphate (DHEAS) levels (SMD: -0.55, 95% CI -0.94 to -0.16, P<0.01).
SGLT-2i use is associated with salutary outcomes of metabolic and anthropometric markers of PCOS and likely favourable hormonal effects.
[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021268564], PROSPERO 2021 CRD42021268564.
Sinha B
，Ghosal S
《Frontiers in Endocrinology》
Dapagliflozin attenuates fat accumulation and insulin resistance in obese mice with polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS), a common endocrine disorder affecting premenopausal women, is associated with various metabolic consequences such as insulin resistance, hyperlipidemia, obesity, and type 2 diabetes mellitus (T2DM). Insulin sensitizers, such as metformin and pioglitazone, though effective, often leads to significant gastrointestinal adverse effects or weight gain, limiting its suitability for women with PCOS. There is an urgent need for safe, effective and affordable agents. Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, enhances glucose elimination through urine, thereby reducing body weight and improving glucose and lipid metabolism. Nevertheless, it is not currently recommended as a therapeutic option for PCOS in clinical guidelines. In this study, we systematically examined the impact of dapagliflozin on an obese PCOS mouse model, focusing on alterations in glucose metabolism, adipose tissue morphology, and plasma lipid profile. Obese PCOS was induced in mice by continuous dihydrotestosterone (DHEA) injections over 21 days and high-fat diet (HFD) feeding. PCOS mice were then orally gavaged with dapagliflozin (1 mg/kg), metformin (50 mg/kg), or vehicle daily for 8 weeks, respectively. Our results demonstrated that dapagliflozin significantly prevented body weight gain and reduced fat mass in obese PCOS mice. Meanwhile, dapagliflozin treatment improved glucose tolerance and increased insulin sensitivity compared to the control PCOS mice. Furthermore, dapagliflozin significantly improved adipocyte accumulation and morphology in white adipose tissue, resulting in a normalized plasma lipid profile in PCOS mice. In conclusion, our results suggest that dapagliflozin is an effective agent in managing glucose and lipid metabolism disorders in obese PCOS mice.
Lin B
，Guo X
，Lu W
，Niu R
，Zeng X
，Chen Z
，Wu C
，Liu C
... -
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