Glucose Intolerance After a Recent History of Gestational DiabetesPhase 3SERENANCT05569772
Semaglutide for the Treatment of Glucose Intolerance in Women With Prior Gestational Diabetes
A Phase 3 study testing Semaglutide Pen Injector in people with Glucose Intolerance After a Recent History of Gestational Diabetes, run by Universitaire Ziekenhuizen KU Leuven at 13 sites in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Glucose Intolerance After a Recent History of Gestational Diabetes
- What is being tested?
- Semaglutide Pen Injector
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 252 participants
- Where
- 13 sitesBelgium
- Study dates
- 14 Sep 2023to May 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
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.
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
Belgium13 sites, 13 recruiting
- Recruiting
AZORG
Aalst
Katrien Wierckx
- Recruiting
UZA
Antwerp
Niels Bochanen
- Recruiting
ZAS
Antwerp
Ann Verhaegen
- Recruiting
AZ St Jan Brugge
Bruges
Sara Vandewalle, MD, 003250 45 23 3, SARA.VANDEWALLE@azsintjan.be
- Recruiting
Erasme
Brussels
Maria Lytrivi
- Recruiting
UZ Brussel
Brussels
Nancy Van Wilder
- Recruiting
Jan Yperman
Ieper
An Nollet, MD, 003257 35 72 70, an.nollet@yperman.net
- Recruiting
AZ Groeninge Kortrijk
Kortrijk
Gertjan Vereecke
- Recruiting
UZ Leuven
Leuven
Katrien Benhalima
- Recruiting
CHU de Liège
Liège
JC Philips
- Recruiting
Centre Hospitalier Mouscron
Mouscron
Philippe Oriot
- Recruiting
Vitaz
Sint-Niklaas
Peter Coremans
- Recruiting
AZ Turnhout
Turnhout
Joke Cuypers, MD, 003214 44 44 32, joke.cuypers@azturnhout.be
About this study
Official title: Semaglutide for the Treatment of Glucose Intolerance in Women With Prior Gestational Diabetes: a Double Blind RCT
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.
Read the detailed description
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®).
Insulin sensitivity and β-cell function
- β-cell function, assessed by HOMA-B, insulinogenic index divided by HOMA-IR, insulin secretion-sensitivity index-2, and the Stumvoll index;
- Insulin sensitivity, assessed by the Matsuda index (reflecting whole body insulin sensitivity) and 1/HOMA-IR, reflecting primarily hepatic insulin sensitivity.
Cardiometabolic risk factors
- Prevalence of the metabolic syndrome;
- Blood pressure (blood pressure ≥140/90 mmHg) and heart rate;
- Lipid profile, including low density lipoprotein-cholesterol (LDL-cholesterol, ≥100 mg/dL or ≥2,6 mmol/L) and triglycerides (≥150 mg/dL or ≥1,7 mmol/L).
Patient-reported outcomes
- Health-related quality of life assessed by SF-36 and EQ-5D-5L;
- Symptoms of depression (CES-D) and anxiety (short-form STAI);
- Treatment satisfaction assessed using a study-specific questionnaire based on the Diabetes Treatment Satisfaction Questionnaire;
- Sleep quality (Pittsburgh Sleep Quality Index) and food security (short-form HFSSM).
Biomarker outcomes
- Changes in and associations of metabolomic profiles, with cardiometabolic risk and treatment response.
Health economic outcomes
- Quality-adjusted life years (QALYs);
- Incremental costs and incremental cost-effectiveness ratio (ICER) of semaglutide compared with placebo.
- Health economic analyses are considered exploratory and hypothesis-generating, as the study was primarily powered for the clinical endpoint of incident T2DM rather than 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.
- Being tested
- Semaglutide Pen Injector, Semaglutide placebo
- Keywords
- gestational diabetes, glucose intolerance postpartum, prevention, type 2 diabetes, GLP-1 agonist, semaglutide
- Medical subject headings
- Diabetes, Gestational, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide Pen InjectorDrug
Also called Ozempic
maintenance dose of 1mg SC once weekly
Semaglutide placeboDrug
maintenance dose of 1mg SC once weekly
| Study group | Role | What they receive |
|---|---|---|
| semaglutide | Active comparator | 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 Receives: Drug: Semaglutide Pen Injector |
| placebo | Placebo comparator | placebo SC once weekly, the same dose-escalation regimen, using matching injections, treatment duration of max. 3 years Receives: Drug: Semaglutide placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of T2DM
Defined by FPG, OGTT, and/or HbA1c according to the ADA criteria
Measured: by 160 weeks
Secondary outcomes (33)
Need for glucose-lowering (rescue) therapy
Percentage need for rescue therapy for diabetes
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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%
Measured: 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%
Measured: 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%
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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).
Measured: 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
Measured: 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
Measured: 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)
Measured: Assessed at 160 weeks (end of treatment) and at 172-184 weeks (3-6 months after discontinuation of study medication)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2022
- Study start14 Sep 2023
- Primary completionMar 2030 (estimated)
- Study completionMay 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glucose Intolerance After a Recent History of Gestational DiabetesStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- multi-centric double blind RCT
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 252 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Antwerp, Universitair Ziekenhuis Brussel, General Hospital Groeninge, Vitaz, Centre Hospitalier Universitaire de Liege, Erasme University Hospital, Centre Hospitalier Mouscron, Jan Yperman Ziekenhuis, AZ Turnhout, AZ Sint-Lucas Brugge, Ziekenhuis aan de Stroom, Onze Lieve Vrouw Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05569772
- Sponsor's protocol ID
- S66967
- Other IDs
- 2022-502082-22-00
- Acronym
- SERENA
- Status last verified
- Sep 2026
- First submitted
- 28 Sep 2022
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Vanlaer Y, Embo N, Bochanen N, Van Wilder N, Vereecke G, Wierckx K, Verhaegen A, Coremans P, Philips JC, Lytrivi M, Oriot P, Vandewalle S, Cuypers J, Deconinck B, Laenen A, Mathieu C, Benhalima K. Semaglutide for prevention of type 2 diabetes in women with postpartum prediabetes after gestational diabetes: protocol for a Belgian multicentre double-blind randomised placebo-controlled trial. BMJ Open. 2026 Jul 23;16(7):e118191. doi: 10.1136/bmjopen-2026-118191.
PubMed 42493207