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Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM

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ClinicalTrials.gov Identifier: NCT01856907
Recruitment Status : Completed
First Posted : May 20, 2013
Results First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Karen Elkind-Hirsch, Woman's

Brief Summary:
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. 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. Studies are needed for optimal postpartum and long-term health of women who have had GDM. 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 DM2. 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 (a DPP-4 inhibitor)-plus metformin is more effective than metformin alone or placebo in improving metabolic parameters, specifically the impact on β-cell function, in prior GDM women with glucose abnormalities.

Condition or disease Intervention/treatment Phase
Disorder of Glucose Regulation Drug: Sitagliptin-Metformin Drug: Metformin Drug: Placebo pill Phase 4

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 : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 28, 2013
Actual Primary Completion Date : September 5, 2017
Actual Study Completion Date : September 28, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sitagliptin-Metformin
50 mg/1000 mg twice a day (BID)
Drug: Sitagliptin-Metformin
Experimental -dipeptidyl peptidase-4 (DPP-4) inhibitor- oral medication
Other Name: Janumet

Placebo Comparator: Placebo pill
1 pill/BID for 16 weeks
Drug: Placebo pill
Will evaluate effect of lifestyle and diet only
Other Name: placebo control

Active Comparator: Metformin
1000 mg BID
Drug: Metformin
Biguanide- insulin sensitizer
Other Name: Glucophage




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Fasting Blood Glucose [ Time Frame: 16 weeks ]
    Blood glucose in the fasting state

  2. 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..

  3. Fasting Insulin Resistance [ Time Frame: 16 weeks ]
    Insulin resistance calculated from fasting glucose and insulin levels known as HOMA-IR

  4. Matsuda Index of Insulin Sensitivity [ Time Frame: 16 weeks ]
    Composite insulin sensitivity index calculated from from glucose and insulin levels obtained during the OGTT

  5. Oral Disposition Index [ Time Frame: 16 weeks ]
    Measure of pancreatic beta cell compensatory action known as IS-SI

  6. Triglyceride/HDL-Cholesterol Ratio [ Time Frame: 16 weeks ]
    The ratio of triglyceride to HDL cholesterol is used as an indirect measure of insulin resistance

  7. Body Mass Index [ Time Frame: 16 weeks ]
    Measure of body weight corrected by height

  8. Waist Circumference [ Time Frame: 16 weeks ]
    Measure of central fat

  9. Waist-to-Height Ratio [ Time Frame: 16 weeks ]
    Measure of central obesity adjusted for stature


Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01856907


Locations
United States, Louisiana
Woman's Hospital
Baton Rouge, Louisiana, United States, 70817
Sponsors and Collaborators
Woman's
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Karen Elkind-Hirsch, Ph.D. Woman's Hospital, Louisiana
Principal Investigator: Martha Paterson, M.D. Woman's Hospital, Louisiana
  Study Documents (Full-Text)

Documents provided by Karen Elkind-Hirsch, Woman's:

Responsible Party: Karen Elkind-Hirsch, Director of Research, Woman's
ClinicalTrials.gov Identifier: NCT01856907     History of Changes
Other Study ID Numbers: RP13-009
First Posted: May 20, 2013    Key Record Dates
Results First Posted: January 23, 2018
Last Update Posted: January 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual data will only be shared with participant

Keywords provided by Karen Elkind-Hirsch, Woman's:
prediabetes
impaired fasting/impaired glucose tolerance
post gestational diabetes
diabetes prevention

Additional relevant MeSH terms:
Metformin
Sitagliptin Phosphate
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action