Semaglutide for the Treatment of Glucose Intolerance in Women with Prior Gestational Diabetes

NCT ID: NCT05569772

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-14
• Study Completion Date: 2028-12-31

Brief 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. 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.

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)] 6-24 weeks 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 glycaemia, OGTT and/or HbA1c according to the ADA criteria. Important secondary endpoints include the need for rescue therapy for diabetes, regression to normoglycaemia, weight loss, beta-cell function, insulin resistance and the metabolic syndrome. 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.

Conditions

Glucose Intolerance After a Recent History of Gestational Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Semaglutide Pen Injector

Intervention Type: DRUG

maintenance dose of 1mg SC once weekly

placebo

placebo SC once weekly, the same dose-escalation regimen, using matching injections, treatment duration of max. 3 years

Group Type: PLACEBO_COMPARATOR

Semaglutide placebo

Intervention Type: DRUG

maintenance dose of 1mg SC once weekly

Interventions

Semaglutide Pen Injector

maintenance dose of 1mg SC once weekly

Intervention Type: DRUG

Semaglutide placebo

maintenance dose of 1mg SC once weekly

Intervention Type: DRUG

Other Intervention Names

Ozempic

Eligibility Criteria

Inclusion Criteria

1. Voluntary written informed consent of the participant has been obtained prior to any screening procedures

2. Use of highly effective methods of birth control

3. History of GDM (diagnosed with 2013 WHO criteria 24-32 weeks of pregnancy) and glucose intolerance 6-24 weeks postpartum (based on the ADA criteria)

4. Needs to be able to understand and speak Dutch, French or English

Exclusion Criteria

• 1. Participant has a history of any type of diabetes or auto-antibodies for type 1 diabetes, history of pancreatitis, family or personal history of medullary thyroid carcinoma or personal history of thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, severe psychiatric disorder in the past year, heart failure NYHA class 4, end-stage renal disease (eGFR <15) or dialysis, or history of bariatric surgery 2. Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol 3. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial 4. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive 5. Participation in an interventional Trial with an investigational medicinal product or device 6. Age <18 years, breastfeeding >24 weeks postpartum or HbA1c≥6.5% at the time of the OGTT in pregnancy 7. Use of medication with significant impact on glycaemia (such as high dose glucocorticoids or metformin)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Antwerp

OTHER

Sponsor Role: collaborator

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: collaborator

General Hospital Groeninge

OTHER

Sponsor Role: collaborator

Onze Lieve Vrouw Hospital

OTHER

Sponsor Role: collaborator

Jessa Hospital

OTHER

Sponsor Role: collaborator

Ziekenhuis Netwerk Antwerpen (ZNA)

OTHER

Sponsor Role: collaborator

Vitaz

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Liege

OTHER

Sponsor Role: collaborator

Erasme University Hospital

OTHER

Sponsor Role: collaborator

Centre Hospitalier Mouscron

UNKNOWN

Sponsor Role: collaborator

Jan Yperman Ziekenhuis

OTHER

Sponsor Role: collaborator

AZ Turnhout

OTHER

Sponsor Role: collaborator

AZ Sint-Lucas Brugge

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

OLV-Aalst-Asse

Aalst, , Belgium

Site Status: RECRUITING

UZA

Antwerp, , Belgium

Site Status: RECRUITING

ZNA,

Antwerp, , Belgium

Site Status: RECRUITING

AZ St Jan Brugge

Bruges, , Belgium

Site Status: RECRUITING

Erasme

Brussels, , Belgium

Site Status: RECRUITING

UZ Brussel

Brussels, , Belgium

Site Status: RECRUITING

Jan Yperman

Ieper, , Belgium

Site Status: RECRUITING

AZ Groeninge Kortrijk

Kortrijk, , Belgium

Site Status: RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status: RECRUITING

CHU de Liège

Liège, , Belgium

Site Status: RECRUITING

Centre Hospitalier Mouscron

Mouscron, , Belgium

Site Status: RECRUITING

Vitaz

Sint-Niklaas, , Belgium

Site Status: RECRUITING

AZ Turnhout

Turnhout, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Katrien Benhalima, MD PhD

Role: CONTACT

katrien.benhalima@uzleuven.be

16340614 ext. 32

Facility Contacts

Katrien Wierckx

Role: primary

Niels Bochanen

Role: primary

Ann Verhaegen

Role: primary

Sara Vandewalle, MD

Role: primary

SARA.VANDEWALLE@azsintjan.be

003250 45 23 3

Maria Lytrivi

Role: primary

Nancy Van Wilder

Role: primary

An Nollet, MD

Role: primary

an.nollet@yperman.net

003257 35 72 70

Gertjan Vereecke

Role: primary

Katrien Benhalima

Role: primary

JC Philips

Role: primary

Philippe Oriot

Role: primary

Peter Coremans

Role: primary

Joke Cuypers, MD

Role: primary

joke.cuypers@azturnhout.be

003214 44 44 32

Other Identifiers

2022-502082-22-00

Identifier Type: OTHER

Identifier Source: secondary_id

S66967

Identifier Type: -

Identifier Source: org_study_id