Incretin Effect in PCOS Women

Inkretineffekten Hos Patienter Med Polycystisk Ovariesyndrom før og Efter Behandling af Insulinresistens (Incretin Effect in Patients With Polycystic Ovary Syndrome Before and After Treatment of Insulin Resistance)

This study investigates the incretin effect in women with polycystic ovary syndrome (PCOS) before and after removal of their insulin resistance by metformin.

The investigators' hypothesis is that insulin resistant women with PCOS have a reduced incretin effect and elevated glucagon responses as measured by a 75-g oral glucose tolerance test and isoglycemic i.v. glucose infusion. The investigators hypothesise that both can be improved when their insulin resistance is removed.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Select A State
    • Hellerup, Select A State, Denmark, 2900
      • Copenhagen University Hospital Gentofte

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria PCOS-women:

• Diagnosed with PCOS according to the Rotterdam criteria
• more than 18 years old
• BMI less than 30 kg/m2
• Normal glucose tolerance and fasting plasma glucose (assessed by 75-g OGTT)
• Negative GAD65 and islet cell autoantibodies
• Insulin resistant according to HOMA-IR
• informed consent

Inclusion Criteria healthy women:

• more than 18 years old
• BMI less than 30 kg/m2
• Normal glucose tolerance and fasting plasma glucose (assessed by 75-g OGTT)
• Negative GAD65 and islet cell autoantibodies
• informed consent
• regular menstrual cycle (28-35 days)
• Plasma androgen levels within reference levels

Exclusion Criteria PCOS and healthy women:

• First or second degree relatives with diabetes
• pregnancy or breast feeding
• treatment with medication which influences the glucose metabolism (incl hormonal contraception)
• Congenital diseases which cause hyperandrogenism and irregular bleeding
• Known adrenal hyperplasia
• Known hyperprolaktinemia
• Alcohol consumption of more than 20 grams a day
• Hemoglobin less than 7.8 %

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin-Placebo; Metformin, 2x 2 tablets a day, 500 mg tablets for 12 weeks, 6 weeks wash-out, 12 weeks placebo	Drug: Metformin; Metformin, 2x 2 tablets a day, 500 mg tablets; Other Names: 657-24-9; Drug: Placebo; Placebo (to metformin)
Placebo Comparator: Placebo-metformin; Placebo tablets, 2x 2 tablets per day for 12 weeks, 6 weeks wash-out, 12 weeks metformin, 2x 2 tablets per day, 500 mg per tablet	Drug: Metformin; Metformin, 2x 2 tablets a day, 500 mg tablets; Other Names: 657-24-9; Drug: Placebo; Placebo (to metformin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in incretin effect from baseline and until after removal of insulin resistance	The incretin effect will be assessed from the insulin secretion during af 75 g OGTT and IIGI at baseline and after 12 weeks' treatment with placebo and metformin	baseline and 12 weeks' treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucagon response	Glucagon responses (plasma concentrations) will be assessed during the 75-g OGTTs	0, 12 and 30 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Louise Vedtofte, MSc., PhD, Copenhagen University hospital, Gentofte

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): November 23, 2017
• Study Completion (Actual): November 23, 2017

Study Registration Dates

• First Submitted: June 11, 2013
• First Submitted That Met QC Criteria: June 30, 2013
• First Posted (Estimate): July 4, 2013

Study Record Updates

• Last Update Posted (Actual): November 27, 2020
• Last Update Submitted That Met QC Criteria: November 24, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: PCOS; insulin resistance; incretin effect; OGTT; IIGI
• 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; Metformin
• Other Study ID Numbers: PCOS-INK