Towards Precision Medicine for Diabetes in Pregnancy (ToPMedDiP)

Rationale: Gestational diabetes is currently treated by the one-size-fits-all-approach. Treatment efficacy is poorly defined and inconsiderate of patients clinical presentation Objective: To characterize the efficacy of pharmacological treatment of gestational diabetes mellitus between patients with distinct metabolic phenotypes Study design: Prospective observational study, in metformin-treatment efficacy is compared between patients with GDM caused by insulin resistance and patients with GDM caused by low insulin secretion.

Study population: A prospective cohort of 103 women with diagnosed gestational diabetes mellitus treated by metformin.

Main study parameters/endpoints: Primary outcomes is the glucose-disposition-index in late pregnancy (35-37 weeks gestation) and requirement for supplemental insulin-treatment. Secondary outcomes include insulin sensitivity (Matsuda-index), insulin secretion (Stumvoll-index), HbA1c, gestational weight gain, body composition, physical activity, eating behavior, plasma biomarkers, glucose control, and maternal and infant pregnancy outcomes.

Study Overview

• Status: Suspended
• Conditions: Gestational Diabetes; Gestational Diabetes Mellitus
• Intervention / Treatment: Drug: Metformin

• Study Type: Observational
• Enrollment (Estimated): 103

Contacts and Locations

Study Locations

• Netherlands
  • Heerlen, Netherlands, 6419PC
    • Zuyderland Medisch Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients, who are screened (selection per EXPECT-calculator risk for GDM >3.5% [26]) and diagnosed with GDM and treated with metformin are eligible. Per current clinical practice (IADPSG/WHO2013), GDM will be diagnosed at 24-28 weeks by a 75g-oral glucose-tolerance-test (OGTT), if plasma glucose concentrations are: fasting >5.1 mmol/L; 1-h >10 mmol/L; or 2-h >8.5 mmol/L.[2, 25] Metformin-treatment is initiated, if plasma glucose concentrations during the OGTT are: fasting >5.3 mmol/L; and postprandial: >7.8 mmol/L.

Description

Inclusion Criteria:

• having a confirmed single, viable pregnancy past 20 weeks gestation.
• assigned to pharmacological (ie metformin) treatment for GDM.

Exclusion Criteria:

• pre-existing diabetes, hypertension (SBP >160 mmHg & DBP >110 mmHg)
• using medication related to study outcomes prior to GDM diagnosis (insulin, metformin, glyburide, systemic steroids, mood stabilizers, ADHD medication)
• smoking or using recreational drugs that may affect pregnancy outcomes

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Low insulin sensitivity; Women will be classified as having low insulin sensitivity, if their Matsuda-index is in the lowest quartile of a reference cohort	Drug: Metformin; All patients are diagnosed with gestational diabetes and treated with metformin (per routine clinical practice
Low insulin secretion; Women will be classified as having low insulin secretion if their Stumvoll-index is in the lowest quartile of a reference cohort	Drug: Metformin; All patients are diagnosed with gestational diabetes and treated with metformin (per routine clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glucose-disposition-index	glucose-disposition-index is calculated as product of Stumvoll- and Matsuda-index, assessed during a 75g-oral glucose tolerance test,	35-37 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	HbA1c concentration	24-28 and 35-37 weeks gestation
Body weight	Fasting body weight, kg	24-28 and 35-37 weeks gestation
Body fat mass	Fasting body fat mass, in kg	24-28 and 35-37 weeks gestation
Physical Activity	Average steps per day, measured over 7-day period using accelerometry	24-28 and 35-37 weeks gestation
Dietary intake	Average energy intake, measured over 7 days using online dietary records	24-28 and 35-37 weeks gestation
Glucose control	Time in range (3-10 mol/l), measured over 7 days using continuous glucose monitors	24-28 and 35-37 weeks gestation
Delivery complications	occurence and type of complications during delivery	Birth
Neonatal body weight	Neonatal body weight	at birth, and at 6 weeks of age
Neonatal body length	Neonatal body length	at birth, and at 6 weeks of age
Insulin treatment	requirement for additional insulin treatment	35-37 weeks gestation

Collaborators and Investigators

• Sponsor: Zuyderland Medisch Centrum
• Investigators: Principal Investigator: Jasper Most, PhD, Zuyderland Medisch Centrum; Principal Investigator: Jonas Ellerbrock, MD, PhDc, Zuyderland Medisch Centrum

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2023
• Primary Completion (Actual): January 31, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: physical activity; insulin sensitivity; metformin; insulin secretion; continuous glucose monitoring
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes, Gestational; Diabetes Mellitus; Pregnancy in Diabetics; Physiological Effects of Drugs; Hypoglycemic Agents; Metformin
• Other Study ID Numbers: NL80773.096.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD may be shared with investigators upon reasonable, detailed and written request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No