A Phase 3 interventional study of Semaglutide Pen Injector and Semaglutide placebo in Glucose Intolerance After a Recent History of Gestational Diabetes, sponsored by Universitaire Ziekenhuizen KU Leuven. Recruiting at 13 sites in Belgium. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by Universitaire Ziekenhuizen KU Leuven · Phase 3, Interventional, and Prevention
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.
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
Insulin sensitivity and β-cell function
Cardiometabolic risk factors
Patient-reported outcomes
Biomarker outcomes
Health economic outcomes
To achieve 80% power, we plan a sample size of 252 to detect an estimated 50% reduction in the risk to develop T2DM between both groups, assuming a 30% loss to follow-up during the study.
877 studies on the registry are indexed under Diabetes, Gestational; 203 are open to participants now.
This study's planned enrollment of 252 is above the median of 110 across 564 interventional studies indexed under Diabetes, Gestational.
Browse Diabetes, Gestational studies →Universitaire Ziekenhuizen KU Leuven is the lead sponsor of 963 studies on the registry; 267 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
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 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 and no use of medication affecting glucose metabolism. Written ICF is obtained prior to any study-related procedures.
Exclusion criteria 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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Drug: Semaglutide Pen Injector
placebo SC once weekly, the same dose-escalation regimen, using matching injections, treatment duration of max. 3 years
Drug: Semaglutide placebo
maintenance dose of 1mg SC once weekly
Also known as: Ozempic
maintenance dose of 1mg SC once weekly
Development of T2DM
Defined by FPG, OGTT, and/or HbA1c according to the ADA criteria
Time frame: by 160 weeks
Need for glucose-lowering (rescue) therapy
Percentage need for rescue therapy for diabetes
Time frame: 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
Percentage of prediabetes based on FPG, OGTT, and/or HbA1c
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Regression to normoglycaemia
Percentage regression to normoglycaemia, based on fasting glycaemia, oral glucose tolerance test and/or HbA1c (ADA criteria)
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Change in body weight
Change in body weight (kg)
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
BMI
Mean BMI (Kg/m2)
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Waist circumference
Mean waist circumference (cm)
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Waist-to-hip ratio
Waist/hip circumference ratio
Time frame: 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
Percentage weight loss ≥5%
Time frame: 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
Percentage weight loss ≥10%
Time frame: 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
Percentage weight loss ≥15%
Time frame: 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®)
Percentage body fat measured by bioelectrical impedance analysis
Time frame: 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
Beta-cell function measured by the HOMA-B index
Time frame: 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
Beta-cell function measured by the by the insulinogenic index divided by HOMA-insulin resistance index
Time frame: 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
Beta-cell function measured by theby the insulin-secretion sensitivity-2 index
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Stumvoll index
Beta-cell function measured by the Stumvoll index
Time frame: 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)
Whole body Insulin sensitivity measured by the insulin sensitivity index of Matsuda
Time frame: 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
The reciprocal of the homeostasis model assessment of insulin resistance (1/HOMA-IR)
Time frame: 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
Percentage of the metabolic syndrome based on the WHO criteria
Time frame: 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)
Percentage blood pressure ≥140/90mmHg
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Heart rate
Mean heart rate
Time frame: 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)
Percentage LDL cholesterol ≥100mg/dl or ≥2,6 mmol/L
Time frame: 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)
Percentage triglycerides ≥150mg/dl or ≥1,7 mmol/L
Time frame: 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
Health-related quality of life assessed using the 36-Item Short Form Health Survey (SF-36). Scores range from 0 to 100, with higher scores indicating better health-related quality of life
Time frame: 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
Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Visual Analogue Scale (EQ VAS). Scores range from 0 to 100, with higher scores indicating better perceived health status
Time frame: 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)
Depressive symptoms assessed using the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Total scores range from 0 to 60, with higher scores indicating more depressive symptoms
Time frame: 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)
Symptoms of anxiety assessed using the 6-item short-form State-Trait Anxiety Inventory (STAI). Total scores range from 20 to 80 after score transformation, with higher scores indicating greater anxiety symptoms
Time frame: 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
Diabetes risk perception assessed using the Diabetes Risk Perception Questionnaire, a validated questionnaire that evaluates perceived risk of developing diabetes
Time frame: 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)
Sleep quality assessed using the validated Pittsburgh Sleep Quality Index (PSQI)
Time frame: 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)
Food security assessed using the short-form Household Food Security Survey Module (HFSSM). Scores indicate the level of food security, with higher scores reflecting greater food insecurity
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Plasma metabolite concentrations
Changes in and associations of metabolomic profiles, with cardiometabolic risk and treatment response. Assessed using metabolomic profiling. Blood samples will be collected at baseline and every 6 months during a 3.5-year follow-up period (study visits).
Time frame: 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)
Quality-adjusted life years (QALYs), calculated as the area under the curve of health-related quality of life utility values over time, where higher values indicate better health outcomes
Time frame: 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
Incremental costs and incremental cost-effectiveness ratio (ICER) of semaglutide versus placebo
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Incremental healthcare costs
Incremental healthcare costs associated with the intervention compared with control, calculated from collected healthcare resource utilization and unit cost data. Currency (e.g., EUR per participant)
Time frame: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Plan to share: Yes — Individual participant data will be made available upon reasonable request after study completion, database lock, unblinding, and publication of the primary results, subject to applicable ethical, legal, and data protection requirements.
Started Sep 2023 (actual). Primary completion is estimated for Mar 2030, 78 months after the start.
Of 14 phase 3 interventional studies under Diabetes, Gestational, half reached primary completion within 57 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 67. This study's planned 78 months is above that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Semaglutide
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