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Completed

NCT Number: NCT01795248

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

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.

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Key information

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen

Hellerup, 2900, Denmark

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

liraglutide

Drug

1.8 mg liraglutide

Other names: Victoza, NN2211

Placebo

Drug

Liraglutide without the GLP-1 analogue

Primary outcomes

  1. Change in glucose tolerance

    Time frame: from baseline to 52 wks, 53 wks, 260 wks, and 261 wks

    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 outcomes

  1. Deterioration in glycaemic status

    Time frame: from baseline to 52 wks, 53, wks, 260 wks, and 261 wks

    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

Other outcomes

  1. Changes in glycated hemoglobin

    Time frame: From baseline to 52 wks and 260 wks

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

  2. Changes in anthropometric measurements

    Time frame: from baseline to 52 and 260 wks

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

  3. Changes in beta cell secretory responses

    Time frame: from baseline to 52, 53, 260, and 261 wks

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

  4. Changes in insulin sensitivity

    Time frame: from baseline to 52, 53, 260, and 261 wks

    assessed by HOMA-IR and Matsuda insulin sensitivity index

  5. Changes in incretin hormone secretion

    Time frame: baseline to 52, 53, 260, and 261 wks

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

  6. Changes in incretin effect

    Time frame: baseline to 52, 53, 260, and 261 wks

    insulin and c-peptide responses after OGTT vs. IIGI

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

    Time frame: baseline to 52 and 260 wks

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

  8. Changes in cardio-metabolic risk measures

    Time frame: baseline to 52 and 260 wks

    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))

  9. Changes in gut microbiota

    Time frame: baseline to 52 and 260 wks

    optional to the main protocol

  10. Changes in subjective appetite

    Time frame: baseline to 52, 53, 260, and 261 wks

    visual analogue scale (VAS)

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

    Time frame: baseline to 52 and 260 wks

    as assessed by validated questionnaires

  12. Change in Quality of life

    Time frame: Baseline to 52 and 260 wks

    Assessed by validated questionnaires (SF-36)

  13. Evaluation of alcohol consumption

    Time frame: baseline to 52 and 260 wks

    By validated questionnaires

  14. Evaluation of microalbuminuria

    Time frame: baseline to 52 to 260 wks

    Predicitve value of biomarkers for detection of microalbuminuria

  15. Evaluation of blindedness of participants and investigators

    Time frame: baseline to 52 wks

    questionnaire and the end of the blinded trial

  16. Changes in bonemarkers

    Time frame: baseline to 52 and 260 wks

Sponsors and collaborators

Lead sponsor

Tina Vilsboll

Other

Collaborators

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

Registry information

Official study title

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

Important dates

Study start
2012
Primary completion
2019
Study completion
2020
First posted
Feb 20, 2013
Registry last updated
Nov 4, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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