Late Metabolic Effects of Metformin Therapy in Gestational Diabetes

NCT02417090 | Completed

• 1 other identifier: DIARA2
• Study Type: observational
• Target: 173
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Gestational Diabetes

Outcome Measures

Primary Outcomes (1)

• Metabolic late effects

  To study possible late effects of gestational diabetes treated with metformin vs insulin

  9 years

Study Arms (2)

Metformin therapy

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

Drug: Metformin

Insulin therapy

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

Drug: Insulin

Interventions

Insulin DRUG

Pregnant women who used insulin to treat gestational diabetes

Also known as: Humalog, Protaphane, Novorapid

Insulin therapy

Metformin DRUG

Pregnant women who used metformin to treat gestational diabetes

Also known as: Diformin retard

Metformin therapy

Eligibility Criteria

• Age: 9 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

9-year old children exposed to insulin or metformin in utero because their mothers had gestational diabetes

You may qualify if:

• 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

You may not qualify if:

• severe congenital malformations

Sponsors & Collaborators

• Turku University Hospital: lead
• Oulu University Hospital: collaborator

Related Publications (7)

• 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.

  PMID: 23020608 BACKGROUND

• 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.

  PMID: 21083860 BACKGROUND

• 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.

  PMID: 18795211 RESULT

• 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.

  PMID: 40544417 DERIVED

• 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.

  PMID: 37267720 DERIVED

• 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.

  PMID: 35274295 DERIVED

• 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.

  PMID: 34738701 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood for DNA extraction

MeSH Terms

Conditions

Diabetes, Gestational

Interventions

Insulin; Insulin Lispro; Insulin Aspart; Metformin

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Short-Acting; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Harri J Niinikoski, MD, PhD

  University of Turku

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Pediatric Endocrinologist, Professor of Nutrition in Medicine.

Study Record Dates

• First Submitted: April 10, 2015
• First Posted: April 15, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: December 11, 2020

Record last verified: 2020-12