- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01856907
Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM
A Randomized Pilot Study Evaluating Combination Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Plus Metformin Compared to Metformin Monotherapy and Placebo on Metabolic Abnormalities in Women With a Recent History of GDM
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Gestational diabetes mellitus (GDM) is defined as "any degree of glucose intolerance with onset or first recognition during pregnancy." GDM is one of the most frequent metabolic disorders occurring during pregnancy. Approximately 7% of all pregnancies in the United States are complicated by gestational diabetes resulting in more than 200,000 cases annually. There is epidemiologic evidence associating GDM with insulin resistance, glucose intolerance, and type 2 diabetes (DM2). Among all the risk factors of diabetes mellitus, the experience of gestational diabetes is the strongest one.
Gestational diabetes is often the culmination of years of unrecognized and unmodified diabetes risk factors that lead to overt and occult clinical manifestations during pregnancy. Systematic reviews of older studies conclude that 35-60% women with gestational diabetes will develop type 2 diabetes at rates much greater than control groups who did not have glucose intolerance during pregnancy. The higher rates were in studies of particular ethnic groups in the U.S. Presently, in the literature, there are described new, more efficient methods of diabetes prevention in groups with a high risk of this disorder, which involve both, lifestyle modification and pharmacological therapies. Lifestyle intervention was found to reduce the incidence of type 2 diabetes by 58% and metformin by 31% as compared with placebo. Studies are needed for optimal postpartum and long-term health of women who have had GDM. Considerable recent evidence suggests that incretin-based therapies may be useful for the treatment of DM2 because continuous administration of glucagon-like peptide 1 (GLP-1) produces substantial improvements in glucose control and ß-cell function in subjects with type 2 diabetes. Inhibition of dipeptidyl peptidase-4 (DPP-4) increases the concentration of GLP-1 and may potentially delay disease progression in GDM considering the ß-cell function improvement in DM2 and ß-cell mass shown to increase in animal models. This study will examine if combination sitagliptin-plus metformin is more effective than metformin alone or placebo in improving metabolic parameters, specifically the impact on β-cell function, in at-risk women with a recent history of GDM.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Louisiana
-
Baton Rouge, Louisiana, United States, 70817
- Woman's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Females 18 years to 42 years of age who experienced gestational diabetes mellitus (GDM) during recent (within 12 months) pregnancy with prediabetic hyperglycemia determined by an oral glucose tolerance test (OGTT) with 75 g glucose postpartum. Study subjects will be inclusive of prior GDM women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT) postpartum.
- Written consent for participation in the study
Exclusion Criteria:
- Cholestasis during the past pregnancy
- Any hepatic diseases in the past (viral hepatitis, toxic hepatic damage, jaundice of unknown etiology)
- Serum aspartate transaminase (AST) and/or alanine aminotransferase (ALT) level exceeding more than twice normal lab values
- Presence of hypersensitivity to sitagliptin or other DPP-4 inhibitor
- Current use of metformin, thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, or weight loss medications (prescription or over the counter [OTC])
- Prior use of medication to treat diabetes except gestational diabetes
- Use of drugs known to exacerbate glucose tolerance
- History of diabetes or prior use of medications to treat diabetes except GDM
- Creatinine clearance less than 60 ml/min
- Pregnancy planned during the coming two years
- Currently lactating
- Patient not willing to use adequate contraception during study period (unless sterilized)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sitagliptin-Metformin
50 mg/1000 mg twice a day (BID)
|
Experimental -dipeptidyl peptidase-4 (DPP-4) inhibitor- oral medication
Other Names:
|
Placebo Comparator: Placebo pill
1 pill/BID for 16 weeks
|
Will evaluate effect of lifestyle and diet only
Other Names:
|
Active Comparator: Metformin
1000 mg BID
|
Biguanide- insulin sensitizer
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Normalization of Glucose Levels
Time Frame: 16 weeks
|
Normalization of glucose in patients with abnormal glucose levels is defined as a fasting glucose level of <100 mg/dL and a 2-hour glucose level following a 75 gram oral glucose load of <140 mg/dL
|
16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fasting Blood Glucose
Time Frame: 16 weeks
|
Blood glucose in the fasting state
|
16 weeks
|
Mean Blood Glucose Level From the Oral Glucose Tolerance Test (OGTT)
Time Frame: 16 weeks
|
The mean blood glucose is calculated by averaging the 4 blood glucose levels measure during a 75 gm oral glucose tolerance test .
This involves summing the glucose levels measured at baseline, and 1/2 hour,1 hour and 2 hours after the glucose load and dividing by 4..
|
16 weeks
|
Fasting Insulin Resistance
Time Frame: 16 weeks
|
Insulin resistance calculated from fasting glucose and insulin levels known as HOMA-IR
|
16 weeks
|
Matsuda Index of Insulin Sensitivity
Time Frame: 16 weeks
|
Composite insulin sensitivity index calculated from from glucose and insulin levels obtained during the OGTT
|
16 weeks
|
Oral Disposition Index
Time Frame: 16 weeks
|
Measure of pancreatic beta cell compensatory action known as IS-SI
|
16 weeks
|
Triglyceride/HDL-Cholesterol Ratio
Time Frame: 16 weeks
|
The ratio of triglyceride to HDL cholesterol is used as an indirect measure of insulin resistance
|
16 weeks
|
Body Mass Index
Time Frame: 16 weeks
|
Measure of body weight corrected by height
|
16 weeks
|
Waist Circumference
Time Frame: 16 weeks
|
Measure of central fat
|
16 weeks
|
Waist-to-Height Ratio
Time Frame: 16 weeks
|
Measure of central obesity adjusted for stature
|
16 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Liver Enzymes as Safety Measure
Time Frame: 16 weeks
|
Number of patients with no clinically significant changes in liver enzymes-measure of liver enzymes was a study safety endpoint
|
16 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Martha Paterson, M.D., Woman's Hospital, Louisiana
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RP13-009
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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