Type 2 DiabetesPhase 3MiTyNCT01353391
Metformin in Women With Type 2 Diabetes in Pregnancy Trial
A Phase 3 study testing Metformin in people with Type 2 Diabetes, run by Mount Sinai Hospital, Canada at 1 site in Canada.
Trial summary
Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, however despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 1 siteCanada
- Study dates
- 25 May 2011to 5 Jun 2019
- Phase
- Phase 3
- 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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women who are between of 18-45 years of age.
- (i). Women diagnosed with type 2 diabetes prior to pregnancy, OR (ii). Women with undiagnosed type 2 diabetes diagnosed prior to 20 weeks gestation, defined as women presenting with gestational diabetes before 20 weeks gestation with various combinations, as per Canadian Diabetes Association, including:
- 2 fasting glucose ≥ 7.0 mmol/L, or
- 2 HbA1c of ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the Diabetes Control and Complications Trial (DCCT) assay, or
- 1 fasting glucose ≥7.0 mmol/L and 1 HbA1c ≥ 0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay, or
- 1 fasting glucose ≥ 7.0 mmol/L and 1 two hour (2 hr) ≥ 11.1 on a 75 g Oral Glucose Tolerance Test (OGTT), or
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- 1 HbA1C ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay and 1 two hour (2 hr) ≥ 11.1 on a 75 g OGTT.
- Pregnancy gestation between 6+0-22+6 weeks.
- Live singleton fetus.
Who cannot join
- Women who are not on insulin. Women who are on oral hypoglycemic agents will be taken off at the start of the trial and started on insulin prior to randomization.
- Diabetes diagnosed after 20 weeks gestation.
- Type 1 diabetes.
- Known intolerance to metformin.
- Contraindications to metformin use which include:
- (i). Renal insufficiency (defined as serum creatinine of greater than 130 µmol/L or creatinine clearance <60 ml/min) , (ii). Moderate to severe liver dysfunction (defined as liver enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) greater than 3 times the upper limit of normal), (iii). Shock or sepsis, and (iv.) Previous hypersensitivity to metformin.
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- Women with significant gastrointestinal problems such as severe vomiting requiring IV fluids or hospitalization, or active Crohn's or colitis.
- Previous participation in the trial. h. Women who have a fetus with a known potentially lethal anomaly will be excluded. Information regarding congenital anomalies diagnosed after randomization will be recorded.
- Known higher order pregnancies (twins, triplets, etc). These women will be excluded as they have a higher rate of adverse outcomes and we want to avoid any inequalities if they are unequally distributed between the groups.
- Presence of acute or chronic metabolic acidosis, including diabetic ketoacidosis.
- History of diabetic ketoacidosis or history of lactic acidosis. l. Presence of excessive alcohol intake, acute or chronic. m. Presence of congestive heart failure or history of congestive heart failure.
Trial locations and contacts
1 site in 1 country.
Canada1 site
The Centre for Mother, Infant, and Child Research, Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5
About this study
Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, however despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, in addition to treatment with insulin, will help with blood sugar control, lower the dose of insulin needed, lower weight gain, and improve baby outcomes.
Read the detailed description
Type 2 diabetes in pregnancy is increasing in prevalence and these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, as an adjunct to insulin, will decrease these adverse outcomes by reducing maternal hyperglycemia, high maternal insulin doses, excessive maternal weight gain and gestational hypertension/pre-eclampsia, all of which should reduce perinatal and neonatal mortality and morbidity. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. This study is an randomized controlled trial (RCT) that adds metformin to insulin, and is a double-blind, placebo-controlled RCT. The investigators believe that neither metformin alone nor insulin alone will effectively treat this population, and therefore our design, which includes the addition of metformin to insulin, will be the most relevant to our patients.
- Conditions
- Type 2 Diabetes
- Being tested
- Metformin, Placebo Comparator
- Keywords
- Diabetes, MiTy, Metformin in Women, Type 2 Diabetes Pregnancy
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
500 mg daily OD from randomisation for 2 weeks, then 1000mg BID throughout the duration of pregnancy
Placebo ComparatorDrug
500 mg daily OD from randomisation for 2 weeks, then 1000mg BID throughout the duration of pregnancy
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Active comparator | Not described Receives: Drug: Metformin |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours.
Measured: conception to 28 days after birth
Secondary outcomes (21)
Large for gestational age (LGA) infants
Defined as greater than the 90th percentile for weight, based on the National canadian fetal growth standards for singleton boys and girls.
Measured: Up to 24 hours after birth
Pregnancy loss
Spontaneous abortion defined as death of a fetus at <20 weeks gestation; Stillbirth defined as death of a fetus with a birth weight ≥ 500g or at ≥ 20 wks gestational age regardless of birth weight; Neonatal death defined as death of a live born infant within the first 28 days of life or prior to hospital discharge, whichever is later.
Measured: Up to 40 weeks gestation
Preterm birth
Birth < 37 weeks gestation
Measured: Up to 37 weeks gestation
Respiratory distress
Given surfactant via an endotracheal tube and/or requiring assisted positive pressure ventilation within 72 hours after birth.
Measured: within 72 hours after birth
Neonatal hypoglycemia
A plasma glucose <2.6 mmol/L on one or more occasions, starting at 30-60 minutes after birth, and necessitating intravenous dextrose within the first 48 hours of life.
Measured: NICU admission >24 hours
NICU admission >24 hours
Admission to a neonatal intensive or special care unit for > 24 hours during the initial hospitalization after birth
Measured: NICU admission >24 hours
Cord blood gases pH <7.0
Measured: Within 4 hours of birth
Hyperinsulinemia as measured by elevated cord blood C-peptide
A cord serum C-peptide value > 1.7 ug/L (which is >90th percentile of values for the total cohort of participants in the HAPO trial) will be defined as hyperinsulinemia.
Measured: Within 4 hours of birth
Maternal glycemic control as measured by HbA1c and capillary glucose measurements.
Gestational age at testing will be recorded. All downloaded glucose results will be transmitted on a regular basis to a central site for future analysis. Monthly correlations will be done with the laboratory during routine monthly blood draws.
Measured: Up to 40 weeks gestation
Maternal hypoglycemia
Maternal hypoglycemia defined as mild (<3.6, symptomatic and asymptomatic or requiring treatment), or severe (loss of consciousness or confusion requiring assistance) will be documented at each visit.
Measured: Up to 40 weeks gestation
Maternal weight gain
The first and last weight will be obtained at the first and last visit in pregnancy, whether they be done by the endocrinologist, family physician or obstetrician.
Measured: Up to 40 weeks gestation
Maternal insulin doses
Maternal insulin doses (overall amount and number of patients that are taking 'high' insulin doses defined as 2 Units/kg or more per day)
Measured: Up to 40 weeks gestation
Pre-eclampsia, and/or gestational hypertension
Gestational hypertension: New onset of hypertension in pregnancy ≥ 20 weeks gestation in a woman with previously normal blood pressure, defined as diastolic blood pressure of ≥ 90 mmHg, taken on 2 occasions or placed on antihypertensive medication and without proteinuria.
Pre-eclampsia: please refer to protocol for definition
Measured: Up to 40 weeks gestation
Sepsis
A positive blood and/or cerebral spinal fluid culture during the neonatal hospital stay.
Measured: Up to 28 days after birth
Hyperbilirubinemia
Significant jaundice was present based on bilirubin levels requiring treatment with phototherapy> 6 continuous hours, or an exchange transfusion, or receiving intravenous gamma globulin, or requiring readmission into hospital during the first 7 days of life.
Measured: First 7 days of life
Number of hospitalizations
Number of hospitalizations prior to admission for delivery and the duration of hospital stays for the mother prior to admission for delivery and associated with delivery.
Measured: Up to 40 weeks gestation
Rate of caesarean-section
Measured: Up to 40 weeks gestation
Duration of hospital stay for infant.
Duration of hospital stay for infant associated with his/her birth until the first discharge home
Measured: Up to 28 days after birth
Fetal fat mass
Fetal fat mass compared with women treated with insulin plus placebo
Measured: Up to 7 days after birth
Birth Injury
Defined as any of the following: spinal cord injury, basal skull fracture or depressed skull fracture, clavicular fracture, long bone fracture, subdural or intracerebral hemorrhage or any kind
Measured: Up to 7 days after birth
Shoulder dystocia
Documentation of any shoulder dystocia in the delivery records, plus 3 or more of the following: McRoberts maneuver, suprapubic maneuver, episiotomy, delivery of the posterior arm, Woods maneuver, Rubins maneuver, All fours Gaskins maneuver, intentional fracture of the clavicle, and/or Zavenelli maneuver.
Measured: At delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2011 (estimated)
- Study start25 May 2011
- Primary completion5 Jun 2019
- Study completion5 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto, Sunnybrook Research Institute, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Denice Feig, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01353391
- Sponsor's protocol ID
- MOP-106678
- Acronym
- MiTy
- Status last verified
- Mar 2020
- First submitted
- 2 May 2011
- Last updated
- 3 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, Fantus IG, Hutton E, Armson AB, Lipscombe LL, Simmons D, Barrett JFR, Karanicolas PJ, Tobin S, McIntyre HD, Tian SY, Tomlinson G, Murphy KE; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020 Oct;8(10):834-844. doi: 10.1016/S2213-8587(20)30310-7.
PubMed 32946820Feig DS, Murphy K, Asztalos E, Tomlinson G, Sanchez J, Zinman B, Ohlsson A, Ryan EA, Fantus IG, Armson AB, Lipscombe LL, Barrett JF; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi-center randomized controlled trial. BMC Pregnancy Childbirth. 2016 Jul 19;16(1):173. doi: 10.1186/s12884-016-0954-4.
PubMed 27435163
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin in Women With Type 2 Diabetes in Pregnancy Trial
- ClinicalTrials.gov ID
- NCT01353391
- Acronym / sponsor ID
- MiTy / MOP-106678
- Conditions
- Type 2 Diabetes
- Keywords
- Diabetes, MiTy, Metformin in Women, Type 2 Diabetes Pregnancy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- University Health Network, Toronto, Sunnybrook Research Institute, Canadian Institutes of Health Research (CIHR)
- Study start
- 25 May 2011 (actual)
- Primary completion
- 5 Jun 2019 (actual)
- Study completion
- 5 Jun 2019 (actual)
- First posted
- 13 May 2011 (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.
Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, however despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, in addition to treatment with insulin, will help with blood sugar control, lower the dose of insulin needed, lower weight gain, and improve baby outcomes.
Detailed description
Type 2 diabetes in pregnancy is increasing in prevalence and these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, as an adjunct to insulin, will decrease these adverse outcomes by reducing maternal hyperglycemia, high maternal insulin doses, excessive maternal weight gain and gestational hypertension/pre-eclampsia, all of which should reduce perinatal and neonatal mortality and morbidity. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. This study is an randomized controlled trial (RCT) that adds metformin to insulin, and is a double-blind, placebo-controlled RCT. The investigators believe that neither metformin alone nor insulin alone will effectively treat this population, and therefore our design, which includes the addition of metformin to insulin, will be the most relevant to our patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Active comparator | Drug: Metformin |
| Placebo | Placebo comparator | Drug: Placebo Comparator |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Women who are between of 18-45 years of age.
- (i). Women diagnosed with type 2 diabetes prior to pregnancy, OR (ii). Women with undiagnosed type 2 diabetes diagnosed prior to 20 weeks gestation, defined as women presenting with gestational diabetes before 20 weeks gestation with various combinations, as per Canadian Diabetes Association, including:
- Pregnancy gestation between 6+0-22+6 weeks.
- Live singleton fetus.
Key exclusion criteria (11 listed)
- Women who are not on insulin. Women who are on oral hypoglycemic agents will be taken off at the start of the trial and started on insulin prior to randomization.
- Diabetes diagnosed after 20 weeks gestation.
- Type 1 diabetes.
- Known intolerance to metformin.
- Contraindications to metformin use which include:
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 |
|---|---|---|
| Metformin500 mg daily OD from randomisation for 2 weeks, then 1000mg BID throughout the duration of pregnancy | Drug | Metformin |
| Placebo Comparator500 mg daily OD from randomisation for 2 weeks, then 1000mg BID throughout the duration of pregnancy | Drug | Placebo |
Primary outcome
A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours.
Time frame: conception to 28 days after birth
21 secondary outcomes
Large for gestational age (LGA) infants
Time frame: Up to 24 hours after birth
Pregnancy loss
Time frame: Up to 40 weeks gestation
Preterm birth
Time frame: Up to 37 weeks gestation
Respiratory distress
Time frame: within 72 hours after birth
Neonatal hypoglycemia
Time frame: NICU admission >24 hours
NICU admission >24 hours
Time frame: NICU admission >24 hours
Cord blood gases pH <7.0
Time frame: Within 4 hours of birth
Hyperinsulinemia as measured by elevated cord blood C-peptide
Time frame: Within 4 hours of birth
Maternal glycemic control as measured by HbA1c and capillary glucose measurements.
Time frame: Up to 40 weeks gestation
Maternal hypoglycemia
Time frame: Up to 40 weeks gestation
Maternal weight gain
Time frame: Up to 40 weeks gestation
Maternal insulin doses
Time frame: Up to 40 weeks gestation
Pre-eclampsia, and/or gestational hypertension
Time frame: Up to 40 weeks gestation
Sepsis
Time frame: Up to 28 days after birth
Hyperbilirubinemia
Time frame: First 7 days of life
Number of hospitalizations
Time frame: Up to 40 weeks gestation
Rate of caesarean-section
Time frame: Up to 40 weeks gestation
Duration of hospital stay for infant.
Time frame: Up to 28 days after birth
Fetal fat mass
Time frame: Up to 7 days after birth
Birth Injury
Time frame: Up to 7 days after birth
Shoulder dystocia
Time frame: At delivery
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 3 Mar 2020.
- Derived from this study: PubMed 32946820Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, Fantus IG, Hutton E, Armson AB, Lipscombe LL, Simmons D, Barrett JFR, Karanicolas PJ, Tobin S, McIntyre HD, Tian SY, Tomlinson G, Murphy KE; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020 Oct;8(10):834-844. doi: 10.1016/S2213-8587(20)30310-7.
- Derived from this study: PubMed 27435163Feig DS, Murphy K, Asztalos E, Tomlinson G, Sanchez J, Zinman B, Ohlsson A, Ryan EA, Fantus IG, Armson AB, Lipscombe LL, Barrett JF; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi-center randomized controlled trial. BMC Pregnancy Childbirth. 2016 Jul 19;16(1):173. doi: 10.1186/s12884-016-0954-4.
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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.
Denice Feig, MD principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin in people with Type 2 Diabetes, run by Mount Sinai Hospital, Canada at 1 site in Canada.
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 9 inclusion and 11 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 3 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours. (time frame: conception to 28 days after birth). 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 NCT01353391, which also lists 2 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 3 Mar 2020.