NCT01234649.

Trial name or title	Effects of Intervention with the Glucagon‐like Peptide 1 (GLP‐1) Analog Liraglutide Plus Metformin Versus Metformin Monotherapy in Overweight/Obese Women with Metabolic Defects and Recent History of Gestational Diabetes Mellitus (GDM)
Methods	Type of trial: efficacy trial Allocation: randomised Intervention model: parallel assignment Masking: double blind (participant, carer, investigator) Primary purpose: prevention
Participants	Condition: obese with previous GDM and IFG, IGT, or both with or without β‐cell dysfunction postpartum requiring pharmacological intervention Enrolment: 150 Inclusion criteria: women age 18‐45 years who experienced GDM within 52 weeks of index pregnancy; actual BMI > 25 kg/ m²; written consent for participation in the trial; women completed lactation; dysglycaemia (IFG, IGT, or both) or β‐cell dysfunction postpartum requiring pharmacological intervention (except T1DM or T2DM), or both Exclusion criteria: personal or family history of medullary thyroid carcinoma or in people with multiple endocrine neoplasia syndrome type 2; history of pancreatitis; significant cardiovascular, cerebrovascular, renal or hepatobiliary diseases (viral hepatitis, toxic hepatic damage, jaundice of unknown aetiology); serum liver enzymes (aspartate aminotransferase or alanine aminotransferase (or both) levels) exceeding more than twice normal laboratory values; uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg, or both); fasting serum triglycerides ≥ 800 mg/dL at screening. Lipid‐lowering medications must have been maintained at the same dose for 3 months prior to enrolment; haematological profiles considered to be clinically significant; cholestasis during past pregnancy; presence of contradictions for GLP‐1 receptor agonist or metformin administration such as allergy or hypersensitivity; current use of metformin, thiazolidinediones, DPP‐4 inhibitors or GLP‐1 receptor agonist medications; use of drugs known to exacerbate glucose tolerance; use of prescription or non‐prescription weight‐loss drugs; diabetes postpartum or history of diabetes or prior use of medications to treat diabetes other than GDM; creatinine clearance < 60 mL/minute; history or currently undergoing chemotherapy or radiotherapy for cancer; pregnancy planned during the coming 2 years; currently breastfeeding; any condition that, in the opinion of investigator, would place the woman at increased risk or otherwise make the women unsuitable for participation in trial
Interventions	Intervention: liraglutide, subcutaneous (titrated up to 1.8 mg) + metformin, PO (titrated up to 1000 mg twice daily) Comparator: placebo, subcutaneous plus metformin, PO (titrated up to 1000 mg twice daily) Duration of intervention: 84 weeks at full dose (8‐12 weeks for up titrate to full dose)
Outcomes	Primary outcomes: index of insulin secretion in relation to insulin resistance will be calculated (change in index from baseline at 32‐36 weeks, 56 ‐60 weeks and study end (80‐84 weeks)). β‐cell compensatory capacity will be evaluated by insulin sensitivity‐secretion index defined as the product of composite insulin sensitivity index and first‐phase insulin release index (insulinogenic index) Secondary outcomes: insulin resistance ‐ baseline (HOMA‐IR) and composite insulin sensitivity index), and pancreatic β‐cell function (corrected insulin response (CIRglupeak) and insulinogenic index/HOMA‐IR (change in indexes from baseline at 32‐36 weeks, 56‐60 weeks, and trial end (80‐84 weeks)). Indexes of insulin sensitivity and secretion using the serum glucose and insulin concentrations obtained in the fasting state and during the 2‐h glucose tolerance test with insulin levels will be computed by several measures previously validated in women. Cardiometabolic risk measures (change in measures (lipids, liver enzymes, blood pressure) from baseline at 32‐36 weeks, 56‐60 weeks and study end (80‐84 weeks). Lipids, liver enzymes, blood pressure. Anthropometric measurements (change in measures of total and central adiposity from baseline at 32‐36 weeks, 56‐60 weeks, and study end (80‐84 weeks)). BMI, absolute body weight, waist circumference, waist:hip ratio. Development of dysglycaemia (changes in glucose tolerance will be evaluated at baseline, 32‐36 weeks, 56‐60 weeks and study end (80‐84 weeks)). Change in glycaemic status from baseline (at 32‐36 weeks, 56‐60 weeks and study end (80‐84 weeks). Dysglycaemia will be defined as IFG, IGT, combined IFG/IGT and diabetic according to the American Diabetes Association. Women diagnosed with diabetes will be withdrawn and referred to a specialised physician Other outcomes: none specified
Starting date	Trial start date: January 2011 Trial completion date: October 2017
Contact information	Responsible party/principal investigator: Karen E Elkind‐Hirsch, PhD and Martha Paterson, MD, Woman's Hospital, Louisiana
Study identifier	NCT number: NCT01234649
Official title	Effects of Intervention with the Glucagon‐like Peptide 1 (GLP‐1) Analog Liraglutide Plus Metformin Versus Metformin Monotherapy in Overweight/Obese Women with Metabolic Defects and Recent History of Gestational Diabetes Mellitus (GDM)
Stated purpose of study	Quote: "This study will examine if the addition of liraglutide to metformin therapy is more effective than metformin alone in improving insulin sensitivity and normalizing insulin secretion in at‐risk overweight/obese women with prior GDM."
Notes	Investigator clarified the intervention period through email correspondence