Clinical trial NCT05569772: Semaglutide for the Treatment of Glucose Intolerance in Women with Prior Gestational Diabetes
Official title: Semaglutide for the Treatment of Glucose Intolerance in Women with Prior Gestational Diabetes: a Double Blind RCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Glucose Intolerance After a Recent History of Gestational Diabetes
Keywords: gestational diabetes
glucose intolerance postpartum
prevention
type 2 diabetes
GLP-1 agonist
semaglutide
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: University Hospital, Antwerp
name: Universitair Ziekenhuis Brussel
name: General Hospital Groeninge
name: Onze Lieve Vrouw Hospital
name: Jessa Hospital
name: Ziekenhuis Netwerk Antwerpen (ZNA)
name: Vitaz
name: Centre Hospitalier Universitaire de Liege
name: Erasme University Hospital
name: Centre Hospitalier Mouscron
name: Jan Yperman Ziekenhuis
name: AZ Turnhout
name: AZ Sint-Lucas Brugge
First posted: 2022-10-06
Enrollment: 252
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multi-centric double blind RCT
Primary purpose: PREVENTION

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.

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)

Primary outcomes:
measure: type 2 diabetes
timeFrame: by 160 weeks
Secondary outcomes:
measure: medication for diabetes
timeFrame: by 160 weeks
measure: prediabetes
timeFrame: by 160 weeks
measure: normoglycaemia
timeFrame: by 160 weeks
measure: BMI
timeFrame: by 160 weeks
measure: waist circumference
timeFrame: by 160 weeks
measure: waist/hip ratio
timeFrame: by 160 weeks
measure: 5% weight loss
timeFrame: by 160 weeks
measure: 10% weight loss
timeFrame: by 160 weeks
measure: 15% weight loss
timeFrame: by 160 weeks
measure: body fat percentage
timeFrame: by 160 weeks
measure: HOMA-B index
timeFrame: by 160 weeks
measure: insulinogenic index
timeFrame: by 160 weeks
measure: ISSI-2 index
timeFrame: by 160 weeks
measure: the Stumvoll index.
timeFrame: by 160 weeks
measure: Matsuda index
timeFrame: by 160 weeks
measure: HOMA-IR
timeFrame: by 160 weeks
measure: metabolic syndrome
timeFrame: by 160 weeks
measure: Hypertension
timeFrame: by 160 weeks
measure: heart rate
timeFrame: by 160 weeks
measure: LDL cholesterol
timeFrame: by 160 weeks
measure: Triglycerides
timeFrame: by 160 weeks
measure: hypoglycaemia
timeFrame: by 160 weeks
measure: gastro-intestinal side effects
timeFrame: by 160 weeks
measure: self-reported quality of life
timeFrame: by 160 weeks
measure: symptoms of depression
timeFrame: by 160 weeks
measure: anxiety
timeFrame: by 160 weeks
measure: Diabetes risk perception
timeFrame: by 160 weeks
measure: sleep quality
timeFrame: by 160 weeks
measure: diabetes remission
timeFrame: by 172-184 weeks (3-6 months after end of therapy)
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: OLV-Aalst-Asse
city: Antwerp
country: Belgium
facility: UZA
city: Antwerp
country: Belgium
facility: ZNA,
city: Brugge
country: Belgium
facility: AZ St Jan Brugge
city: Brussel
country: Belgium
facility: Erasme
city: Brussel
country: Belgium
facility: UZ Brussel
city: Ieper
country: Belgium
facility: Jan Yperman
city: Kortrijk
country: Belgium
facility: AZ Groeninge Kortrijk
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU de Liège
city: Mouscron
country: Belgium
facility: Centre Hospitalier Mouscron
city: Sint-Niklaas
country: Belgium
facility: Vitaz
city: Turnhout
country: Belgium
facility: AZ Turnhout
Study officials:
References: