Semaglutide for the Treatment of Glucose Intolerance in Women With Prior Gestational Diabetes: a Double Blind RCT
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 252
- 试验地点
- 18
- 主要终点
- type 2 diabetes
研究概览
简要总结
Gestational diabetes (GDM) is an important contributor to the increasing prevalence of type 2 diabetes (T2DM). Women with glucose intolerance in early postpartum are a particularly high-risk group with about 50% who will develop T2DM within 5 years after the delivery. Moreover, women with a history of GDM progress more rapidly to T2DM compared to women with similarly elevated glucose levels. Early intervention after the index pregnancy is therefore crucial to prevent T2DM. With the SERENA project, the investigators aim to reduce the risk to develop T2DM with the long-acting GLP-1 agonist semaglutide in women with a recent history of GDM and glucose intolerance in early postpartum.
详细描述
Patient population: Women with a recent history of gestational diabetes (GDM) and persistent glucose intolerance in early postpartum are a particularly high risk group, with about 50% developing type 2 diabetes (T2DM) within 5 years after the delivery. Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) agonist with multiple beneficial metabolic effects, including glucose lowering effect, weight loss and cardiovascular protective effects. The investigators hypothesize that in women with prior GDM and glucose intolerance in early postpartum, treatment with semaglutide will reduce the risk to develop T2DM on the long-term compared to placebo.
Intervention and comparison: Belgian multi-centric double blind RCT with 13 centers to compare semaglutide (once weekly) with placebo in women with a recent history of GDM and glucose intolerance [impaired fasting glycaemia (IFG) and/or impaired glucose tolerance (IGT)] 6weeks - 12 months postpartum. Participants will be 1/1 randomized to semaglutide or placebo on a background of lifestyle measures. Semaglutide will be uptitrated to 1mg/week over a 8-week period. Participants will be followed-up for 3 years. Participants will receive a 75g oral glucose tolerance test (OGTT) 3-6 months after the stop of the intervention. Randomization will be stratified according to BMI at the early postpartum visit (<25; 25-29.9 and ≥30Kg/m²).
Outcomes: The primary endpoint is the development of T2DM by 160 weeks defined by fasting plasma glucose, OGTT and/or HbA1c according to the ADA criteria. Important secondary endpoints are assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication) and include:
Glycaemic outcomes
- Need for glucose-lowering (rescue) therapy;
- Frequency of prediabetes based on FPG, OGTT, and/or HbA1c;
- Regression to normoglycaemia. Anthropometric and body composition outcomes
- Change in body weight, BMI, waist circumference, waist-to-hip ratio;
- Proportion of participants achieving ≥5%, ≥10%, and ≥15% weight loss;
- Body fat percentage assessed by bioelectrical impedance analysis (Bodystat 1500®).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Eligible participants are women aged ≥18 years, with a history of GDM diagnosed according to the 2013 WHO criteria (at 24-32 weeks gestation or <24 weeks for early GDM). Participants must have prediabetes diagnosed between 6 weeks and 12 months postpartum according to ADA criteria (FPG 5.6-6.9 mmol/L, 2-hour OGTT glucose 7.8-11.0 mmol/L and/or HbA1c 39-46 mmol/mol [5.7-6.4%]).
- •Additional inclusion criteria include cessation of breastfeeding, no intention to become pregnant within the next year, use of effective contraception and no use of medication affecting glucose metabolism. Written ICF is obtained prior to any study-related procedures.
排除标准
- •include established diabetes, presence of autoantibodies suggestive of type 1 diabetes, normal glucose tolerance, history of pancreatitis, previous bariatric surgery or planned surgery within two years, unable to understand and speak Dutch, French or English and current pregnant or planning to become pregnant within one year after participating in the study.
研究组 & 干预措施
placebo
placebo SC once weekly, the same dose-escalation regimen, using matching injections, treatment duration of max. 3 years
干预措施: Semaglutide placebo (Drug)
semaglutide
semaglutide SC once weekly, up titration over 2 month period to 1mg/week (0.25mg once weekly, after 4 weeks 0.5mg once weekly and after 8 weeks the maintenance dose of 1mg once weekly), treatment duration of max. 3 years
干预措施: Semaglutide Pen Injector (Drug)
结局指标
主要结局
type 2 diabetes
时间窗: by 160 weeks
development of type 2 diabetes defined by fasting glycaemia, oral glucose tolerance test and/or HbA1c according to the ADA criteria
Development of T2DM
时间窗: by 160 weeks
Defined by FPG, OGTT, and/or HbA1c according to the ADA criteria
次要结局
- medication for diabetes(by 160 weeks)
- prediabetes(by 160 weeks)
- normoglycaemia(by 160 weeks)
- BMI(by 160 weeks)
- waist circumference(by 160 weeks)
- waist/hip ratio(by 160 weeks)
- 5% weight loss(by 160 weeks)
- 10% weight loss(by 160 weeks)
- 15% weight loss(by 160 weeks)
- body fat percentage(by 160 weeks)
- HOMA-B index(by 160 weeks)
- insulinogenic index(by 160 weeks)
- ISSI-2 index(by 160 weeks)
- the Stumvoll index.(by 160 weeks)
- Matsuda index(by 160 weeks)
- HOMA-IR(by 160 weeks)
- metabolic syndrome(by 160 weeks)
- Hypertension(by 160 weeks)
- heart rate(by 160 weeks)
- LDL cholesterol(by 160 weeks)
- Triglycerides(by 160 weeks)
- hypoglycaemia(by 160 weeks)
- gastro-intestinal side effects(by 160 weeks)
- self-reported quality of life(by 160 weeks)
- symptoms of depression(by 160 weeks)
- anxiety(by 160 weeks)
- Diabetes risk perception(by 160 weeks)
- sleep quality(by 160 weeks)
- diabetes remission(by 172-184 weeks (3-6 months after end of therapy))
- Need for glucose-lowering (rescue) therapy(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Frequency of prediabetes based on FPG, OGTT, and/or HbA1c(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Regression to normoglycaemia(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Change in body weight(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- BMI(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Waist circumference(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Waist-to-hip ratio(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Proportion of participants achieving ≥5% weight loss(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Proportion of participants achieving ≥10% weight loss(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Proportion of participants achieving ≥15% weight loss(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Body fat percentage assessed by bioelectrical impedance analysis (Bodystat 1500®)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- β-cell function, assessed by HOMA-B(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Insulinogenic index divided by HOMA-IR(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Insulin secretion-sensitivity index-2(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Stumvoll index(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Insulin sensitivity, assessed by the Matsuda index (reflecting whole body insulin sensitivity)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- 1/HOMA-IR, reflecting primarily hepatic insulin sensitivity(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Prevalence of the metabolic syndrome(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Blood pressure (blood pressure ≥140/90 mmHg)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Heart rate(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Lipid profile, including low density lipoprotein-cholesterol (LDL-cholesterol, ≥100 mg/dL or ≥2,6 mmol/L)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Lipid profile, including triglycerides (≥150 mg/dL or ≥1,7 mmol/L)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Health-related quality of life assessed by SF-36(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Health-related quality of life assessed by EQ-5D-5L(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Symptoms of depression (CES-D)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Symptoms of anxiety (short-form STAI)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Treatment satisfaction assessed using a study-specific questionnaire based on the Diabetes Treatment Satisfaction Questionnaire(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Sleep quality (Pittsburgh Sleep Quality Index)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Food security (short-form HFSSM)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Plasma metabolite concentrations(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Quality-adjusted life years (QALYs)(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Incremental costs and incremental cost-effectiveness ratio (ICER) of semaglutide compared with placebo(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))
- Incremental healthcare costs(Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication))