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

Study Overview
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Brief Summary
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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.

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

Conditions
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Gestational Diabetes Mellitus

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br>1.8 mg liraglutide, subcutaneous, once-daily for five years | Drug: Liraglutide<br>* 1.8 mg liraglutide<br>* Other names: NN2211;|
| Placebo Comparator: Placebo<br>Placebo, subcutaneous, once-daily for one year | Drug: Placebo<br>* Liraglutide without the GLP-1 analogue<br>|
| No Intervention: Control<br>Control without previous GDM. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | from baseline to 52 wks, 53 wks, 260 wks, and 261 wks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | from baseline to 52 wks, 53, wks, 260 wks, and 261 wks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gestational diabetes mellitus, incretin, glucose homeostasis, GLP-1, type 2 diabetes mellitus, liraglutide, Victoza