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

Universitaire Ziekenhuizen KU Leuven

Status and phase: Enrolling; Phase 3

Conditions: Glucose Intolerance After a Recent History of Gestational Diabetes

Treatments: Drug: Semaglutide placebo; Drug: Semaglutide Pen Injector

Study type: Interventional

Funder types: Other

Identifiers

NCT05569772

2022-502082-22-00 (Other Identifier)

S66967

Details and patient eligibility

About

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.

Full 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.

Enrollment: 252 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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252 participants in 2 patient groups, including a placebo group

semaglutide

Active Comparator group

Description:

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

Treatment:

Drug: Semaglutide Pen Injector

placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Semaglutide placebo