Metformin Use to Improve Pregnancy Outcome in Women With Type 1 Diabetes.

NCT ID: NCT03765359

Last Updated: 2023-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-05
• Study Completion Date: 2022-12-19

Brief Summary

The study investigates whether additional metformin medication in combination with regular insulin treatment will decrease the need of insulin for women with diabetes mellitus type 1 during pregnancy.

Detailed Description

Insulin resistance during pregnancy of diabetes mellitus type 1 patients (DM1) increases the need for insulin and makes it more difficult to maintain normoglycemia. Fetal exposure to hyperglycemia induces macrosomia which increases fetal and neonatal morbidity and mortality. Further more obesity and excess weight gain during pregnancy enhances insulin resistance and it's an independent risk factor for fetal macrosomia.

Metformin is a medical treatment for type 2 diabetes (DM2) where consequential pathophysiology includes insulin resistance. It reduces hepatic glucose production and enhances the use of glucose in muscles relieving insulin resistance. Metformin has also found to inhibit weight gain effectively.

Metformin has approved to be safe and effective in patients with gestational diabetes (GDM). It has found to reduce weight gain and improve postprandial blood glucose levels during pregnancy and reduce neonatal birth trauma in GDM. However, there are no previous studies about the use of metformin in pregnant women with DM1.

Two hundred women with DM1 will be randomized to get placebo or metformin in addition to regular insulin treatment. The sample size has been estimated to demonstrate the difference of 15 % in the need to increase insulin dosages during the pregnancy between the study groups.

Conditions

Diabetic Pregnancy; Insulin Resistance; Type1diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

metforminhydrochloride

Metformin medication starts on 12-14 weeks of gestation. The starting dosage is 1 tablet (500 mg) x1 and it is increased gradually 1 tablet a week up to 2+2 tablets (2000mg) daily. Duration of the treatment is approximately until one week before delivery. Otherwise metformin treatment combined with regular insulin and follow-up during pregnancy follows the national guidelines.

Group Type: ACTIVE_COMPARATOR

metforminhydrochloride

Intervention Type: DRUG

metformin 500 mg tablets and insulin

Placebo Oral Tablet

Placebo tablets starts on 12-14 weeks of gestation. The starting dosage is 1 tablet x1 and it is increased gradually 1 tablet a week up to 2+2 tablets daily. Duration of the treatment is approximately until one week before delivery. Otherwise placebo treatment combined with regular insulin and follow-up during pregnancy follows the national guidelines.

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Placebo tablets mimic metformin 500 mg tablets and insulin

Interventions

metforminhydrochloride

metformin 500 mg tablets and insulin

Intervention Type: DRUG

Placebo Oral Tablet

Placebo tablets mimic metformin 500 mg tablets and insulin

Intervention Type: DRUG

Other Intervention Names

A10BA02; Diformin; Metformin

Eligibility Criteria

Inclusion Criteria

• a pregnancy of a woman with type 1 diabetes.

Exclusion Criteria

• multiple pregnancy, significant underlying disease (hearth disease, kidney transplant, IBD (inflammatory bowel disease ), SLE (systemic lupus erythematosus ), diseases with use of high dosage corticosteroids (severe asthma or rheumatic disease), severe complications of diabetes (nephropathy, neuropathy, gastroparesis or severe retinopathy), substance abuse, smoking, BMI <18, strong early pregnancy nausea (=hyperemesis)

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Turku University Hospital

OTHER_GOV

Sponsor Role: collaborator

Oulu University Hospital

OTHER

Sponsor Role: collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role: collaborator

Central Finland Hospital District

OTHER

Sponsor Role: collaborator

Tampere University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kati Tihtonen, PhD

Role: PRINCIPAL_INVESTIGATOR

Tampere University Hospital, Tampere University

Locations

Helsinki University Hospital

Helsinki, , Finland

Central Finland Health Care District

Jyväskylä, , Finland

Oulu University hospital

Oulu, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Hospital

Turku, , Finland

Countries

Finland

References

Juuma E, Tihtonen K, Metso SE, Hannula PM, Helminen M, Tertti K, Immonen H, Georgiadis L, Vayrynen K, Ahtiainen P, Nikkinen H, Koivikko M, Laivuori H, Uotila J. The Effect of Metformin on Insulin Requirement, Glycaemic Control and Weight Gain in Type 1 Diabetes During Pregnancy-a Randomised, Placebo-Controlled Multicentre Study. Diabetes Metab Res Rev. 2025 Sep;41(6):e70085. doi: 10.1002/dmrr.70085.

Reference Type: DERIVED

PMID: 40916351 (View on PubMed)

Other Identifiers

2016-005031-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Diabetes2017

Identifier Type: -

Identifier Source: org_study_id