Clinical trial NCT01795248: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gestational Diabetes Mellitus
Keywords: gestational diabetes mellitus
incretin
glucose homeostasis
GLP-1
type 2 diabetes mellitus
liraglutide
Victoza
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: Rigshospitalet, Denmark
name: Hvidovre University Hospital
name: Herlev Hospital
name: Hillerod Hospital, Denmark
name: University of Copenhagen
name: The Novo Nordisk Foundation Center for Basic Metabolic Research
name: Aarhus University Hospital
First posted: 2013-02-20
Enrollment: 105
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Change in glucose tolerance
timeFrame: from baseline to 52 wks, 53 wks, 260 wks, and 261 wks
Secondary outcomes:
measure: Deterioration in glycaemic status
timeFrame: from baseline to 52 wks, 53, wks, 260 wks, and 261 wks
Other outcomes:
measure: Changes in glycated hemoglobin
timeFrame: From baseline to 52 wks and 260 wks
measure: Changes in anthropometric measurements
timeFrame: from baseline to 52 and 260 wks
measure: Changes in beta cell secretory responses
timeFrame: from baseline to 52, 53, 260, and 261 wks
measure: Changes in insulin sensitivity
timeFrame: from baseline to 52, 53, 260, and 261 wks
measure: Changes in incretin hormone secretion
timeFrame: baseline to 52, 53, 260, and 261 wks
measure: Changes in incretin effect
timeFrame: baseline to 52, 53, 260, and 261 wks
measure: Changes in presence of non-alcoholic fatty liver disease (NAFLD)
timeFrame: baseline to 52 and 260 wks
measure: Changes in cardio-metabolic risk measures
timeFrame: baseline to 52 and 260 wks
measure: Changes in gut microbiota
timeFrame: baseline to 52 and 260 wks
measure: Changes in subjective appetite
timeFrame: baseline to 52, 53, 260, and 261 wks
measure: Number of participants with treatment-related adverse events (Safety and tolerability)
timeFrame: baseline to 52 and 260 wks
measure: Change in Quality of life
timeFrame: Baseline to 52 and 260 wks
measure: Evaluation of alcohol consumption
timeFrame: baseline to 52 and 260 wks
measure: Evaluation of microalbuminuria
timeFrame: baseline to 52 to 260 wks
measure: Evaluation of blindedness of participants and investigators
timeFrame: baseline to 52 wks
measure: Changes in bonemarkers
timeFrame: baseline to 52 and 260 wks
Locations:
city: Hellerup
country: Denmark
facility: Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen
Study officials:
affiliation: University Hospital Gentofte
name: Tina Vilsbøll, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Gentofte
name: Signe Foghsgaard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Steno Diabetes Center Copenhagen
name: Emilie Skytte Andersen, MD, PhD-student
role: PRINCIPAL_INVESTIGATOR
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