Gestational Diabetes Mellitus
Conditions
Keywords
gestational diabetes mellitus, incretin, glucose homeostasis, GLP-1, type 2 diabetes mellitus, liraglutide, Victoza
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.
Interventions
DRUGLiraglutide
1.8 mg liraglutide
DRUGPlacebo
Liraglutide without the GLP-1 analogue
Sponsors
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
Tina Vilsboll
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in glucose tolerance | 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
| Measure | Time frame | Description |
|---|---|---|
| Deterioration in glycaemic status | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in glycated hemoglobin | 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. |
| Changes in anthropometric measurements | from baseline to 52 and 260 wks | Changes in body mass index (BMI)(kg/m2), absolute body weight (kg), and waist:hip ratio |
| Changes in beta cell secretory responses | 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 |
| Changes in insulin sensitivity | from baseline to 52, 53, 260, and 261 wks | assessed by HOMA-IR and Matsuda insulin sensitivity index |
| Changes in incretin hormone secretion | 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 |
| Changes in incretin effect | baseline to 52, 53, 260, and 261 wks | insulin and c-peptide responses after OGTT vs. IIGI |
| Changes in presence of non-alcoholic fatty liver disease (NAFLD) | 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 |
| Change in Quality of life | Baseline to 52 and 260 wks | Assessed by validated questionnaires (SF-36) |
| Changes in gut microbiota | baseline to 52 and 260 wks | optional to the main protocol |
| Changes in subjective appetite | baseline to 52, 53, 260, and 261 wks | visual analogue scale (VAS) |
| Number of participants with treatment-related adverse events (Safety and tolerability) | baseline to 52 and 260 wks | as assessed by validated questionnaires |
| Evaluation of microalbuminuria | baseline to 52 to 260 wks | Predicitve value of biomarkers for detection of microalbuminuria |
| Evaluation of blindedness of participants and investigators | baseline to 52 wks | questionnaire and the end of the blinded trial |
| Changes in bonemarkers | baseline to 52 and 260 wks | — |
| Changes in cardio-metabolic risk measures | 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)) |
| Evaluation of alcohol consumption | baseline to 52 and 260 wks | By validated questionnaires |
Countries
Denmark
Outcome results
None listed