SGLT2 Inhibitors in Patients With PCOS

Shanghai 10th People's Hospital68 enrolled

Overview

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with a prevalence of 5% to 15% in premenopausal women. Patients with PCOS presents as abnormal menstruation, ovulation disorders and/or hyperandrogenemia, and often accompanied by insulin resistance and other metabolic abnormalities. Metformin has been clarified as an option in patients with PCOS. However, the clinical responses to metformin are limited and different. Sodium glucose co-transporter 2 (SGLT2) inhibitors are novel drugs for the treatment of type 2 diabetes, with weight loss, reducing insulin resistance and cardiovascular benefits. Limited data is available on the efficacy of SGLT2 inhibitors in patients with PCOS.

This clinical study aims to determine the safety and efficacy of canagliflozin vs metformin in Polycystic Ovary Syndrome (PCOS) patients with insulin resistance (IR). Methods: A single center, prospective, randomized open-label study (ratio 1:1), non-inferiority trial was conducted in the department of endocrinology, Shanghai Tenth People's Hospital between July 2019 and April 2021. PCOS women aged 18-45 years with IR were enrolled and randomly assigned to either canagliflozin 100 mg (n = 33) or metformin 1500-2000 mg (n = 35) daily for 12 weeks. The primary outcome was changes in HOMA-IR after 12 weeks treatment. The secondary outcomes included changes in anthropometric, menstrual frequency, sex hormone and metabolic parameters.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Polycystic Ovary Syndrome

Interventions

SGLT2 inhibitorsDRUG

Sodium-glucose cotransporters inhibitors (SGLT2i) are novel hypoglycemic drugs with unique hypoglycemic mechanisms, which are completely independent of islet β-cell function or insulin sensitivity. Previous studies have shown that SGLT2i may improve IR by inhibiting glucotoxicity, reducing body weight, reducing inflammation, improving islet β-cell function, and reducing oxidative stress.

MetforminDRUG

Metformin is a classic drug for the treatment of polycystic ovary syndrome, which can improve the degree of insulin resistance in PCOS patients.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion criteria: * Fmale aged 18- 45; * Meet Rotterdam criteria; * Insulin Rsistance Exclusion Criteria: * Women who are pregnant or have a pregnancy plan within six months; ·Congenital adrenocortical hyperplasia; * Hyperprolactinemia; * Hyperthyroidism or hypothyroidism; * Abnormal liver function (≥ 3 times of the upper limit of normal range); * Abnormal renal function (GFR\<60ml/min/1.73m2); * Adrenal or ovarian tumors secreting androgens; * Used contraceptives, metformin, GLP-1RA, SGLT2I, pioglitazone and contraceptives in the last 3 month.

Locations (1)

Shanghai Tenth People' Hospital

Shanghai, Shanghai Municipality, China

Outcomes

Primary Outcomes

HOMA-IR

Homeostatic model assessment insulin resistance index

Time frame: 3 months

Secondary Outcomes

WHR

Waist/hip Ratio

Time frame: 3 months

Waist Circumference (cm）

Time frame: 3 months

Hip Circumference（cm）

Time frame: 3 months

Menstrual cycles

annual number of menstrual cycles

Time frame: 3 months

FBG

fasting blood-glucose in mmol/L

Time frame: 3 months

PBG

postprandial blood-glucose in mmol/L

Time frame: 3 months

FINS

fasting serum insulin in mU/L

Time frame: 3 months

PINS

Postprandial insulin in mU/L

Time frame: 3 months

ALT

alanine aminotransferase in U/L

Time frame: 3 months

AST

Aspartate aminotransferase in U/L

Time frame: 3 months

Uric acid in umol/L

Time frame: 3 months

Creatinine in umol/L

Time frame: 3 months

LDL-c

low-density lipoprotein cholesterol in mmol/L

Time frame: 3 months

HDL-c

high-density lipoprotein cholesterol in mmol/L

Time frame: 3 months

Total Cholesterol in mmol/L

Time frame: 3 months

Triglyceride in mmol/L

Time frame: 3 months

total testosterone in nmol/L

Time frame: 3 months

Luteinizing hormone in IU/L

Time frame: 3 months

FSH

follicle-stimulating hormone in IU/L）

Time frame: 3 months

Estradiol in pmol/L、PRL(Prolactin in uIU/ml)

Time frame: 3 months

PRL

Prolactin in uIU/ml

Time frame: 3 months

Metabonomics

the change of Metabonomics after the treatment

Time frame: 3 months

Ferriman-Gallwey score

Ferriman-Gallwey score、acne, male pattern baldness

Time frame: 3 months

acne score

male pattern baldness

Time frame: 3 months

male pattern baldness

Time frame: 3 months

HOMA- ISI

Homeostatic model assessment insulin sensitivity index

Time frame: 3 months

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Adverse events and Safety data in two treatment groups.

Time frame: 3 months

BMI

body mass index in kg/m\^2

Time frame: 3 months

SHBG

sex hormone binding globulin in nmol/L

Time frame: 3 months

Free testosterone in pg/ml

Time frame: 3 months

DHEAS

Dehydroepiandrosterone Sulfate in ug/dl

Time frame: 3 months

Androstenedione in ng/ml

Time frame: 3 months

Data from ClinicalTrials.gov

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