Gestational DiabetesDIARA2NCT02417090
Late Metabolic Effects of Metformin Therapy in Gestational Diabetes
An observational study of Gestational Diabetes, run by Turku University Hospital.
Trial 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… Read more about this study
- Who is it for?
- Ages 9 to 10 years
- Conditions the study is for
- Gestational Diabetes
- What is being tested?
- Insulin and Metformin
- How many people
- 173 participants
- Where
- No sites listed yet
- Study dates
- May 2015to 1 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 to 10 years
- All sexes
- No healthy volunteers
- Child
Study population: 9-year old children exposed to insulin or metformin in utero because their mothers had gestational diabetes
Who may be able to join
- 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
Who cannot join
- severe congenital malformations
About this study
Official title: Metformin Therapy for Gestational Diabetes - Metabolic Late Effects on Child at 9 Years of Age
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.
Read the detailed description
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
- Gestational Diabetes
- Medical subject headings
- Diabetes, Gestational
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InsulinDrug
Also called Humalog, Protaphane, Novorapid
Pregnant women who used insulin to treat gestational diabetes
MetforminDrug
Also called Diformin retard
Pregnant women who used metformin to treat gestational diabetes
| Study group | Role | What they receive |
|---|---|---|
| Metformin therapy | 9-year-old children whose mothers used metformin for gestational diabetes Receives: Drug: Metformin | |
| Insulin therapy | 9-year-old children whose mothers used insulin for gestational diabetes Receives: Drug: Insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic late effects
To study possible late effects of gestational diabetes treated with metformin vs insulin
Measured: 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2015 (estimated)
- Study startMay 2015
- Primary completion1 Dec 2019
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Gestational DiabetesStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 173 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Collaborators
- Oulu University Hospital
- Responsible party
- Principal investigator, Harri Niinikoski, Turku University Hospital
- Investigators
- Harri J Niinikoski, MD, PhD, Principal investigator, University of Turku
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02417090
- Sponsor's protocol ID
- DIARA2
- Acronym
- DIARA2
- Status last verified
- Dec 2020
- First submitted
- 10 Apr 2015
- Last updated
- 11 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23020608Ijas 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.
PubMed 21083860Tertti 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.
PubMed 18795211Huhtala 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.
PubMed 40544417Huhtala 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.
PubMed 37267720Huhtala 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.
PubMed 35274295Paavilainen 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.
PubMed 34738701
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin Therapy for Gestational Diabetes - Metabolic Late Effects on Child at 9 Years of Age
- ClinicalTrials.gov ID
- NCT02417090
- Acronym / sponsor ID
- DIARA2 / DIARA2
- Conditions
- Gestational Diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 173 participants (actual)
- Lead sponsor
- Turku University HospitalOther government
- Collaborators
- Oulu University Hospital
- Study start
- May 2015
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 15 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin therapy | – | Drug: Metformin9-year-old children whose mothers used metformin for gestational diabetes |
| Insulin therapy | – | Drug: Insulin9-year-old children whose mothers used insulin for gestational diabetes |
Who may qualify
- Ages
- 9 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- 9-year old children exposed to insulin or metformin in utero because their mothers had gestational diabetes
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- severe congenital malformations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InsulinAlso: Humalog, Protaphane, NovorapidPregnant women who used insulin to treat gestational diabetes | Drug | Insulin therapy |
| MetforminAlso: Diformin retardPregnant women who used metformin to treat gestational diabetes | Drug | Metformin therapy |
Primary outcome
Metabolic late effects
Time frame: 9 years
To study possible late effects of gestational diabetes treated with metformin vs insulin
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2020.
- Background: PubMed 23020608Tertti 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.
- Background: PubMed 21083860Ijas 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.
- Results publication: PubMed 18795211Tertti 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.
- Derived from this study: PubMed 40544417Huhtala 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.
- Derived from this study: PubMed 37267720Huhtala 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.
- Derived from this study: PubMed 35274295Huhtala 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.
- Derived from this study: PubMed 34738701Paavilainen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harri J Niinikoski, MD, PhD principal investigator
University of Turku
Questions about this trial
What is this clinical trial studying?
An observational study of Gestational Diabetes, run by Turku University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic late effects (time frame: 9 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02417090, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2020.