Late Metabolic Effects of Metformin Therapy in Gestational Diabetes

NCT ID: NCT02417090

Last Updated: 2020-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

173 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-05-31

Study Completion Date

2019-12-01

Brief Summary

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Metformin in widely used as the treatment of gestational diabetes. However, it is not known whether exposure to metformin in utero has late metabolic effects on the child.

In this study the investigators investigate metabolism (oral glucose tolerance test, insulin, plasma lipoproteins, inflammation markers as well as body composition by DEXA (dual energy X-ray absorption) and MRI) in 9 year-old children whose mothers used either metformin of insulin during pregnancy.

Detailed Description

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Gestational diabetes is usually managed with diet and insulin, if needed. However, oral metformin therapy has been also used to treat gestational diabetes and the short-term studies have shown that it is effective and also safe for the child. However, long-term studies of its effects are lacking.

Previously, several years ago, 217 pregnant women with gestational diabetes in Turku and 100 such women in Oulu, Finland, were randomised to either insulin or metformin therapy to treat gestational diabetes. In those studies, the metformin therapy proved to be safe in the short-term.

Now these children are 5-9 years old. In the present study these children (as well as their mothers) are investigated when the children are 9 years old. The aim is to study whether the metformin given during the pregnancy has any metabolic effects on the child at 9 years of age. To do this these families are contacted by mail and asked to participate into the study.

At 9 years of age, the following investigations will be made (after consent from the child and family): oral glucose tolerance test+insulin+c-peptide, plasma lipoproteins, adiponectin, PAI-1 (plasminogen activator inhibitor-1), IL-6 (interleukin-6), HS CRP (high-sensitivity C-reactive protein), p-metabolomics, DEXA, abdominal MRI, WISC IV (Wechsler intelligence scale for children IV)cognitive testing, BRIEF questionnaire, questionnaire about diet and health habits. The study subjects will also be clinically examined and measured and blood pressure will be taken.

All analyses are performed at the University hospital laboratory and radiology facilities using modern techniques. The amount of blood taken is limited and also radiation dose from DEXA is very small. The data are kept behind lock and key. Statistical analyses will be performed to study whether children exposed to metformin during pregnancy have any differences in their metabolism and well-being than those exposed to insulin. This study involves no new medical treatments to the study subjects.

Conditions

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Gestational Diabetes

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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Metformin therapy

9-year-old children whose mothers used metformin for gestational diabetes

Metformin

Intervention Type DRUG

Pregnant women who used metformin to treat gestational diabetes

Insulin therapy

9-year-old children whose mothers used insulin for gestational diabetes

Insulin

Intervention Type DRUG

Pregnant women who used insulin to treat gestational diabetes

Interventions

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Insulin

Pregnant women who used insulin to treat gestational diabetes

Intervention Type DRUG

Metformin

Pregnant women who used metformin to treat gestational diabetes

Intervention Type DRUG

Other Intervention Names

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Humalog, Protaphane, Novorapid Diformin retard

Eligibility Criteria

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Inclusion Criteria

* all children whose mothers used either metformin or insulin to treat gestational diabetes and were involved in the previous metformin study in Turku or Oulu, Finland

Exclusion Criteria

* severe congenital malformations
Minimum Eligible Age

9 Years

Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Oulu University Hospital

OTHER

Sponsor Role collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Harri Niinikoski

MD, Pediatric Endocrinologist, Professor of Nutrition in Medicine.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Harri J Niinikoski, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Turku

References

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Tertti K, Ekblad U, Koskinen P, Vahlberg T, Ronnemaa T. Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes Obes Metab. 2013 Mar;15(3):246-51. doi: 10.1111/dom.12017. Epub 2012 Oct 24.

Reference Type BACKGROUND
PMID: 23020608 (View on PubMed)

Ijas H, Vaarasmaki M, Morin-Papunen L, Keravuo R, Ebeling T, Saarela T, Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study. BJOG. 2011 Jun;118(7):880-5. doi: 10.1111/j.1471-0528.2010.02763.x. Epub 2010 Nov 18.

Reference Type BACKGROUND
PMID: 21083860 (View on PubMed)

Tertti K, Ekblad U, Vahlberg T, Ronnemaa T. Comparison of metformin and insulin in the treatment of gestational diabetes: a retrospective, case-control study. Rev Diabet Stud. 2008 Summer;5(2):95-101. doi: 10.1900/RDS.2008.5.95. Epub 2008 Aug 10.

Reference Type RESULT
PMID: 18795211 (View on PubMed)

Huhtala M, Ronnemaa T, Tertti K, Niinikoski H, Paavilainen E. Maternal and umbilical cord serum lipids in gestational diabetes predict offspring insulin secretion and resistance at the age of nine years. Metabolomics. 2025 Jun 22;21(4):87. doi: 10.1007/s11306-025-02281-9.

Reference Type DERIVED
PMID: 40544417 (View on PubMed)

Huhtala MS, Ronnemaa T, Paavilainen E, Niinikoski H, Pellonpera O, Juhila J, Tertti K. Prediction of pre-diabetes and type 2 diabetes nine years postpartum using serum metabolome in pregnant women with gestational diabetes requiring pharmacological treatment. J Diabetes Complications. 2023 Jul;37(7):108513. doi: 10.1016/j.jdiacomp.2023.108513. Epub 2023 May 26.

Reference Type DERIVED
PMID: 37267720 (View on PubMed)

Huhtala M, Nikkinen H, Paavilainen E, Niinikoski H, Vaarasmaki M, Loo BM, Ronnemaa T, Tertti K. Comparison of glucose metabolism and anthropometry in women with previous gestational diabetes treated with metformin vs. insulin: 9-year follow-up of two randomized trials. Acta Obstet Gynecol Scand. 2022 May;101(5):514-523. doi: 10.1111/aogs.14343. Epub 2022 Mar 11.

Reference Type DERIVED
PMID: 35274295 (View on PubMed)

Paavilainen E, Tertti K, Nikkinen H, Veijola R, Vaarasmaki M, Loo BM, Tossavainen P, Ronnemaa T, Niinikoski H. Metformin versus insulin therapy for gestational diabetes: Effects on offspring anthropometrics and metabolism at the age of 9 years: A follow-up study of two open-label, randomized controlled trials. Diabetes Obes Metab. 2022 Mar;24(3):402-410. doi: 10.1111/dom.14589. Epub 2021 Nov 24.

Reference Type DERIVED
PMID: 34738701 (View on PubMed)

Other Identifiers

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DIARA2

Identifier Type: -

Identifier Source: org_study_id