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

Phase 3RecruitingNCT05569772

Universitaire Ziekenhuizen KU Leuven252 enrolled

Overview

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 \[impaired fasting glycaemia (IFG) and/or impaired glucose tolerance (IGT)\] 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.

Study Type

INTERVENTIONAL

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (13)

OLV-Aalst-Asse

Aalst, Belgium

RECRUITING

UZA

Antwerp, Belgium

RECRUITING

ZNA,

Antwerp, Belgium

RECRUITING

AZ St Jan Brugge

Bruges, Belgium

RECRUITING

Erasme

Brussels, Belgium

RECRUITING

UZ Brussel

Brussels, Belgium

RECRUITING

Jan Yperman

Ieper, Belgium

RECRUITING

AZ Groeninge Kortrijk

Kortrijk, Belgium

RECRUITING

UZ Leuven

Leuven, Belgium

RECRUITING

CHU de Liège

Liège, Belgium

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

type 2 diabetes

development of type 2 diabetes defined by fasting glycaemia, oral glucose tolerance test and/or HbA1c according to the ADA criteria

Time frame: by 160 weeks

Secondary Outcomes

medication for diabetes

percentage need for rescue therapy for diabetes

Time frame: by 160 weeks

prediabetes

percentage prediabetes based on fasting glycaemia, oral glucose tolerance test and/or HbA1c (ADA criteria)

Time frame: by 160 weeks

normoglycaemia

percentage regression to normoglycaemia, based on fasting glycaemia, oral glucose tolerance test and/or HbA1c (ADA criteria)

Time frame: by 160 weeks

BMI

mean BMI (Kg/m2)

Time frame: by 160 weeks

waist circumference

mean waist circumference (cm)

Time frame: by 160 weeks

waist/hip ratio

waist/hip circumference ratio

Time frame: by 160 weeks

5% weight loss

percentage weight loss ≥5%

Time frame: by 160 weeks

10% weight loss

percentage weight loss ≥10%

Time frame: by 160 weeks

15% weight loss

percentage weight loss ≥15%

Time frame: by 160 weeks

body fat percentage

percentage body fat measured by bioelectrical impedance analysis

Time frame: by 160 weeks

HOMA-B index

Beta-cell function measured by the HOMA-B index

Time frame: by 160 weeks

insulinogenic index

Beta-cell function measured by the by the insulinogenic index divided by HOMA-insulin resistance index

Time frame: by 160 weeks

ISSI-2 index

Beta-cell function measured by theby the insulin-secretion sensitivity-2 index

Time frame: by 160 weeks

the Stumvoll index.

Beta-cell function measured by the Stumvoll index.

Time frame: by 160 weeks

Matsuda index

whole body Insulin sensitivity measured by the insulin sensitivity index of Matsuda

Time frame: by 160 weeks

HOMA-IR

the reciprocal of the homeostasis model assessment of insulin resistance (1/HOMA-IR)

Time frame: by 160 weeks

metabolic syndrome

percentage of the metabolic syndrome based on the WHO criteria

Time frame: by 160 weeks

Hypertension

percentage blood pressure ≥140/90mmHg

Time frame: by 160 weeks

heart rate

mean heart rate

Time frame: by 160 weeks

LDL cholesterol

percentage LDL cholesterol ≥100mg/dl

Time frame: by 160 weeks

Triglycerides

percentage triglycerides ≥150mg/dl

Time frame: by 160 weeks

hypoglycaemia

percentage with hypoglycaemia (\<54mg/dl)

Time frame: by 160 weeks

gastro-intestinal side effects

percentage nausea, vomiting or diarrhea

Time frame: by 160 weeks

self-reported quality of life

health-related quality of life by SF-36 questionnaire

Time frame: by 160 weeks

symptoms of depression

the 20-item Center for Epidemiologic Studies-Depression (CES-D) questionnaire

Time frame: by 160 weeks

anxiety

six-item short-form of the State-Trait Anxiety Inventory questionnaire on anxiety (STAI)

Time frame: by 160 weeks

Diabetes risk perception

Diabetes Risk perception questionnaire, a validated questionnaire to evaluate the perception to develop diabetes

Time frame: by 160 weeks

sleep quality

The validated Pittsburg sleep quality index to evaluate sleep quality

Time frame: by 160 weeks

diabetes remission

diabetes remission rate after treatment stop, defined by fasting, OGTT and/or HbA1c

Time frame: by 172-184 weeks (3-6 months after end of therapy)

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

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts