SGLT2 Inhibitors in Patients With PCOS (PCOS)

The Efficacy of Canagliflozin Versus Metformin in Women With Polycystic Ovary Syndrome: A Randomized, Open Label Trial

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: SGLT2 inhibitors; Drug: Metformin

Detailed Description

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
• Enrollment (Actual): 68
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Shanghai Tenth People' Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SGLT2 inhibitors group; Intervention with SGLT2 inhibitors (100mg/d) for 3 months	Drug: SGLT2 inhibitors; 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.; Other Names: Canagliflozin tablets or Glucophage
Active Comparator: Metformin group; Intervention with metformin (1500-2000mg/d) for 3 months	Drug: Metformin; Metformin is a classic drug for the treatment of polycystic ovary syndrome, which can improve the degree of insulin resistance in PCOS patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR	Homeostatic model assessment insulin resistance index	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WHR	Waist/hip Ratio	3 months
WC	Waist Circumference (cm）	3 months
HC	Hip Circumference（cm）	3 months
Menstrual cycles	annual number of menstrual cycles	3 months
FBG	fasting blood-glucose in mmol/L	3 months
PBG	postprandial blood-glucose in mmol/L	3 months
FINS	fasting serum insulin in mU/L	3 months
PINS	Postprandial insulin in mU/L	3 months
ALT	alanine aminotransferase in U/L	3 months
AST	Aspartate aminotransferase in U/L	3 months
UA	Uric acid in umol/L	3 months
CR	Creatinine in umol/L	3 months
LDL-c	low-density lipoprotein cholesterol in mmol/L	3 months
HDL-c	high-density lipoprotein cholesterol in mmol/L	3 months
TC	Total Cholesterol in mmol/L	3 months
TG	Triglyceride in mmol/L	3 months
TT	total testosterone in nmol/L	3 months
LH	Luteinizing hormone in IU/L	3 months
FSH	follicle-stimulating hormone in IU/L）	3 months
E2	Estradiol in pmol/L、PRL(Prolactin in uIU/ml)	3 months
PRL	Prolactin in uIU/ml	3 months
Metabonomics	the change of Metabonomics after the treatment	3 months
Ferriman-Gallwey score	Ferriman-Gallwey score、acne, male pattern baldness	3 months
acne score	male pattern baldness	3 months
male pattern baldness	male pattern baldness	3 months
HOMA- ISI	Homeostatic model assessment insulin sensitivity index	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.	3 months
BMI	body mass index in kg/m^2	3 months
SHBG	sex hormone binding globulin in nmol/L	3 months
FT	Free testosterone in pg/ml	3 months
DHEAS	Dehydroepiandrosterone Sulfate in ug/dl	3 months
AD	Androstenedione in ng/ml	3 months

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital

Publications and helpful links

General Publications

• Javed Z, Papageorgiou M, Deshmukh H, Rigby AS, Qamar U, Abbas J, Khan AY, Kilpatrick ES, Atkin SL, Sathyapalan T. Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. Clin Endocrinol (Oxf). 2019 Jun;90(6):805-813. doi: 10.1111/cen.13968. Epub 2019 Apr 2.

Helpful Links

• Efficacy of canagliflozin versus metformin in women with polycystic ovary syndrome: A randomized, open-label, noninferiority trial
• Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: a randomized controlled study

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): April 28, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 6, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Canagliflozin; Polycystic ovary syndrome (PCOS);; Insulin resistance (IR); Sodium-glucose co-transporter-2 inhibitors (SGLT-2i)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Metformin; Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin
• Other Study ID Numbers: SGLT2i PCOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No