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The Impact of Liraglutide on Glucose Tolerance and the Risk of Type 2 Diabetes in Women With Previous Pregnancy-induced Diabetes

Primary Purpose

Gestational Diabetes Mellitus

Status

Completed

Phase

Phase 4

Locations

Denmark

Study Type

Interventional

Intervention

Liraglutide

Placebo

About this trial

This is an interventional prevention trial for Gestational Diabetes Mellitus focused on measuring gestational diabetes mellitus, incretin, glucose homeostasis, GLP-1, type 2 diabetes mellitus, liraglutide, Victoza

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria for women with previous GDM:

Informed oral and written consent
Previous diagnosis of GDM according to current Danish guidelines (mainly PG concentrationa t 120 min after 75 g OGTT ≥ 9.0 mM) during pregnancy within the last 5 years
Age >18 years
25 kg/m2 < BMI < 45 kg/m2
NGT, IFG and or IGT
Safe contraception and negative pregnancy test

Exclusion Criteria for women with previous GDM:

Patients with diabetes
HbA1c ≥6.5%
Patients with previous pancreatitis or previous neoplasia
Pregnant or breast feeding women
Anaemia (haemoglobin <7 mM)
Women planning to become pregnant within the next 5 years
Women using other contraception than intrauterine device (IUD) or oral contraceptives. Women who do not use safe contraception will be offered application of an IUD.
Women treated with statins, corticosteroids or other hormone therapy (except estrogens and gestagens)
Ongoing abuse of alcohol or narcotics
Impaired hepatic function (liver transaminases >3 times upper normal limit)
Impaired renal function (se-creatinine >120 μM and/or albuminuria)
Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >100 mmHg)
Any condition that the investigator feels would interfere with trial participation
Receiving any investigational drug within the last 3 months

Inclusion criteria for women without previous GDM:

Informed oral and written consent
Age >18 years
25 kg/m2 < BMI < 45 kg/m2
NGT
Safe contraception and negative pregnancy test
Pregnancy within the last ten years without GDM

Exclusion Criteria for women without previous GDM :

Pregnant or breast feeding women
Anaemia (haemoglobin <7 mM)

Inclusion Criteria for women without previous GDM and without NAFLD:

Informed oral and written consent
Age >18 years
25 kg/m2 < BMI < 45 kg/m2
NGT
At least one pregnancy witin the last ten years without GDM

Exclusion Criteria for women without previous GDM and without NAFLD:

Pregnant or breast feeding women
Anaemia (haemoglobin <7 mM)
Steatosis as assessed by ultrasound scanning
Recieving any investigational drug within the last 3 months
Any condition that the investigator feels would interfere with the trial participation

Inclusion Criteria for women with biopsi-verified NAFLD:

Informed oral and written consent
Women with known NAFLD or NASH
Age >18 years
25 kg/m2 < BMI < 45 kg/m2
NGT
At least one prior pregnancy

Exclusion Criteria for women with biopsi-verified NAFLD:

women with established cirrhosis
Pregnant or breast feedning women
Anaemia (haemoglobin <7 mM)
Women treated with statins, corticosteroids or other hormone therapy ( except oestrogens and gestagens)
Ongoing abuse of alcohol or narcotics
Impaired renal function (se-creatinine > 120 μM and/or albuminuria)
Uncontrolled hypertension (systolic blood pressure > 180 mmHg, diastolic blood presure > 100 mmHg)
Any condition that the investigator feels would interfere with trial participation

Sites / Locations

Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

No Intervention

Arm Label

Liraglutide

Placebo

Control

Arm Description

1.8 mg liraglutide, subcutaneous, once-daily for five years

Placebo, subcutaneous, once-daily for one year

Control without previous GDM.

Outcomes

Primary Outcome Measures

Change in glucose tolerance

Changes in glucose is measured by area under the curve for the plasma glucose excursion following a 4-hour 75 g oral glucose tolerance test (OGTT)

Secondary Outcome Measures

Deterioration in glycaemic status

Percentage of subjects in each treatment arm with normal glucose tolerance (NGT) at inclusion who develop impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) or type 2 diabetes; or with IFG or IGT who develop combined IFG/IGT; or with combined IFG/IGT who develop type 2 diabetes

Full Information

NCT ID

NCT01795248

First Posted

February 18, 2013

Last Updated

November 3, 2020

Sponsor

Tina Vilsboll

Collaborators

Novo Nordisk A/S, Rigshospitalet, Denmark, Hvidovre University Hospital, Herlev Hospital, Hillerod Hospital, Denmark, University of Copenhagen, The Novo Nordisk Foundation Center for Basic Metabolic Research, Aarhus University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01795248

Brief Title

The Impact of Liraglutide on Glucose Tolerance and the Risk of Type 2 Diabetes in Women With Previous Pregnancy-induced Diabetes

Official Title

The Impact of Liraglutide on Glucose Tolerance and the Risk of Type 2 Diabetes in Women With Previous Gestational Diabetes Mellitus

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

July 2012 (Actual)

Primary Completion Date

September 2019 (Actual)

Study Completion Date

September 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Tina Vilsboll

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

It is well-known that women with previous gestational diabetes mellitus are in risk of developing type 2 diabetes later in life; approximately half of the women develop overt type 2 diabetes within the first 10 years after pregnancy. Knowing this, we want to examine the effect of the type 2 diabetes medicine, liraglutide (Victoza), in women with previous gestational diabetes with the aim of reducing the risk of developing type 2 diabetes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gestational Diabetes Mellitus

Keywords

gestational diabetes mellitus, incretin, glucose homeostasis, GLP-1, type 2 diabetes mellitus, liraglutide, Victoza

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

105 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Liraglutide

Arm Type

Experimental

Arm Description

1.8 mg liraglutide, subcutaneous, once-daily for five years

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo, subcutaneous, once-daily for one year

Arm Title

Control

Arm Type

No Intervention

Arm Description

Control without previous GDM.

Intervention Type

Drug

Intervention Name(s)

Liraglutide

Other Intervention Name(s)

Victoza, NN2211

Intervention Description

1.8 mg liraglutide

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Liraglutide without the GLP-1 analogue

Primary Outcome Measure Information:

Title

Change in glucose tolerance

Description

Changes in glucose is measured by area under the curve for the plasma glucose excursion following a 4-hour 75 g oral glucose tolerance test (OGTT)

Time Frame

from baseline to 52 wks, 53 wks, 260 wks, and 261 wks

Secondary Outcome Measure Information:

Title

Deterioration in glycaemic status

Description

Time Frame

from baseline to 52 wks, 53, wks, 260 wks, and 261 wks

Other Pre-specified Outcome Measures:

Title

Changes in glycated hemoglobin

Description

Changes in glycated hemoglobin (HbA1c). From normoglycaemic to prediabetic or type 2 diabetic and from prediabetic to type 2 diabetic or normoglycaemic.

Time Frame

From baseline to 52 wks and 260 wks

Title

Changes in anthropometric measurements

Description

Changes in body mass index (BMI)(kg/m2), absolute body weight (kg), and waist:hip ratio

Time Frame

from baseline to 52 and 260 wks

Title

Changes in beta cell secretory responses

Description

changes in area under the curve during OGTT and isoglycemic intravenous glucose infusion (IIGI), the homeostatic model assessment (HOMA) and pro-insulin ratio

Time Frame

from baseline to 52, 53, 260, and 261 wks

Title

Changes in insulin sensitivity

Description

assessed by HOMA-IR and Matsuda insulin sensitivity index

Time Frame

from baseline to 52, 53, 260, and 261 wks

Title

Changes in incretin hormone secretion

Description

measured as fasting plasma concentrations and plasma responses of GLP-1, GLP2, and GIP and plasma glucagon during OGTT

Time Frame

baseline to 52, 53, 260, and 261 wks

Title

Changes in incretin effect

Description

insulin and c-peptide responses after OGTT vs. IIGI

Time Frame

baseline to 52, 53, 260, and 261 wks

Title

Changes in presence of non-alcoholic fatty liver disease (NAFLD)

Description

gamma-glutamyltranferase (GGT), intra-heptic fat, FGF-21, whole body and visceral fat mass/fat-free mass, circulating lipids, ultrasound scan and fibroscan

Time Frame

baseline to 52 and 260 wks

Title

Changes in cardio-metabolic risk measures

Description

pro-collagen 3, GGT, Intra-hepatic fat, whole body and visceral fat mass/fat-free mass, circulating lipids and cardiovascular biomarkers (highly sensitive c-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), tumor necrosis factor-alpha (TNF-alpha), adiponectin and plasminogen activator inhibior-1 (PAI-1))

Time Frame

baseline to 52 and 260 wks

Title

Changes in gut microbiota

Description

optional to the main protocol

Time Frame

baseline to 52 and 260 wks

Title

Changes in subjective appetite

Description

visual analogue scale (VAS)

Time Frame

baseline to 52, 53, 260, and 261 wks

Title

Number of participants with treatment-related adverse events (Safety and tolerability)

Description

as assessed by validated questionnaires

Time Frame

baseline to 52 and 260 wks

Title

Change in Quality of life

Description

Assessed by validated questionnaires (SF-36)

Time Frame

Baseline to 52 and 260 wks

Title

Evaluation of alcohol consumption

Description

By validated questionnaires

Time Frame

baseline to 52 and 260 wks

Title

Evaluation of microalbuminuria

Description

Predicitve value of biomarkers for detection of microalbuminuria

Time Frame

baseline to 52 to 260 wks

Title

Evaluation of blindedness of participants and investigators

Description

questionnaire and the end of the blinded trial

Time Frame

baseline to 52 wks

Title

Changes in bonemarkers

Time Frame

baseline to 52 and 260 wks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria for women with previous GDM: Informed oral and written consent Previous diagnosis of GDM according to current Danish guidelines (mainly PG concentrationa t 120 min after 75 g OGTT ≥ 9.0 mM) during pregnancy within the last 5 years Age >18 years 25 kg/m2 < BMI < 45 kg/m2 NGT, IFG and or IGT Safe contraception and negative pregnancy test Exclusion Criteria for women with previous GDM: Patients with diabetes HbA1c ≥6.5% Patients with previous pancreatitis or previous neoplasia Pregnant or breast feeding women Anaemia (haemoglobin <7 mM) Women planning to become pregnant within the next 5 years Women using other contraception than intrauterine device (IUD) or oral contraceptives. Women who do not use safe contraception will be offered application of an IUD. Women treated with statins, corticosteroids or other hormone therapy (except estrogens and gestagens) Ongoing abuse of alcohol or narcotics Impaired hepatic function (liver transaminases >3 times upper normal limit) Impaired renal function (se-creatinine >120 μM and/or albuminuria) Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >100 mmHg) Any condition that the investigator feels would interfere with trial participation Receiving any investigational drug within the last 3 months Inclusion criteria for women without previous GDM: Informed oral and written consent Age >18 years 25 kg/m2 < BMI < 45 kg/m2 NGT Safe contraception and negative pregnancy test Pregnancy within the last ten years without GDM Exclusion Criteria for women without previous GDM : Pregnant or breast feeding women Anaemia (haemoglobin <7 mM) Inclusion Criteria for women without previous GDM and without NAFLD: Informed oral and written consent Age >18 years 25 kg/m2 < BMI < 45 kg/m2 NGT At least one pregnancy witin the last ten years without GDM Exclusion Criteria for women without previous GDM and without NAFLD: Pregnant or breast feeding women Anaemia (haemoglobin <7 mM) Steatosis as assessed by ultrasound scanning Recieving any investigational drug within the last 3 months Any condition that the investigator feels would interfere with the trial participation Inclusion Criteria for women with biopsi-verified NAFLD: Informed oral and written consent Women with known NAFLD or NASH Age >18 years 25 kg/m2 < BMI < 45 kg/m2 NGT At least one prior pregnancy Exclusion Criteria for women with biopsi-verified NAFLD: women with established cirrhosis Pregnant or breast feedning women Anaemia (haemoglobin <7 mM) Women treated with statins, corticosteroids or other hormone therapy ( except oestrogens and gestagens) Ongoing abuse of alcohol or narcotics Impaired renal function (se-creatinine > 120 μM and/or albuminuria) Uncontrolled hypertension (systolic blood pressure > 180 mmHg, diastolic blood presure > 100 mmHg) Any condition that the investigator feels would interfere with trial participation

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tina Vilsbøll, MD, DMSc

Organizational Affiliation

University Hospital Gentofte

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Signe Foghsgaard, MD, PhD

Organizational Affiliation

University Hospital Gentofte

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Emilie Skytte Andersen, MD, PhD-student

Organizational Affiliation

Steno Diabetes Center Copenhagen

Official's Role

Principal Investigator

Facility Information:

Facility Name

Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen

City

Hellerup

ZIP/Postal Code

2900

Country

Denmark

12. IPD Sharing Statement

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Links:

URL

http://gentoftehospital.dk

Description

Main website for the University Hospital Gentofte

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The Impact of Liraglutide on Glucose Tolerance and the Risk of Type 2 Diabetes in Women With Previous Pregnancy-induced Diabetes

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