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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionDisorder of Glucose Regulation
InterventionDrug: Sitagliptin-Metformin
Drug: Metformin
Drug: Placebo pill
PhasePhase 4
SponsorBC Women's Hospital & Health Centre
Responsible PartyBC Women's Hospital & Health Centre
ClinicalTrials.gov IdentifierNCT01856907
First ReceivedMay 14, 2013
Last UpdatedDecember 18, 2013
Last verifiedDecember 2013

Tracking Information[ + expand ][ + ]

First Received DateMay 14, 2013
Last Updated DateDecember 18, 2013
Start DateSeptember 2013
Estimated Primary Completion DateDecember 2014
Current Primary Outcome Measures
  • ß-cell compensatory function [Time Frame: Change from baseline to 16 weeks] [Designated as safety issue: No]• Improving ß-cell compensatory function by enhancing insulin release after an oral glucose load (following the OGTT) and thus improve or delay a decline in glucose tolerance estimated by the disposition index defined as the product of insulin action (Matsuda index) and insulin secretion (insulinogenic index) derived from the OGTT (SIOGTT x Δinsulin30-0 min to glucose30-0 min).
  • Surrogate measures of insulin sensitivity and secretion [Time Frame: Change from baseline to 16 weeks] [Designated as safety issue: No]•Improving markers of insulin sensitivity and secretion after an oral glucose load as measured by the Matsuda index and early insulin response adjusted for insulin sensitivity (insulinogenic index/homeostasis model assessment of insulin resistance [HOMA-IR])
  • Fasting and 2 hour glucose levels after glucose load [Time Frame: Change from baseline to 16 weeks] [Designated as safety issue: No]Correcting glucose control as evaluated by fasting and 2 hour glucose levels after an OGTT
Current Secondary Outcome MeasuresCardiometabolic risk factors [Time Frame: Change from baseline to 16 weeks] [Designated as safety issue: No]We will further examine whether the addition of sitagliptin to metformin therapy is more beneficial than metformin alone or placebo in altering the development or progression of select cardiometabolic risk factors as measured by changes in lipids and blood pressure

Descriptive Information[ + expand ][ + ]

Brief TitleSitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM
Official TitleA 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
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.
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 TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
ConditionDisorder of Glucose Regulation
InterventionDrug: Sitagliptin-Metformin
Experimental -DPP-4 inhibitor- oral medication
Other Names:
JanumetDrug: Metformin
Biguanide- insulin sensitizer
Other Names:
GlucophageDrug: Placebo pill
Will evaluate effect of lifestyle and diet only
Other Names:
placebo control
Study Arm (s)
  • Experimental: Sitagliptin-Metformin
    50 mg/1000 mg BID
  • Placebo Comparator: Placebo pill
    1 pill/BID for 16 weeks
  • Active Comparator: Metformin
    1000 mg BID

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment36
Estimated Completion DateDecember 2014
Estimated Primary Completion DateAugust 2014
Eligibility 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)
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Karen Elkind-Hirsch, Ph.D.
225-231-5278
karen.elkind-hirsch@womans.org
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01856907
Other Study ID NumbersRP13-009
Has Data Monitoring CommitteeYes
Information Provided ByBC Women's Hospital & Health Centre
Study SponsorBC Women's Hospital & Health Centre
CollaboratorsMerck Sharp & Dohme Corp.
Investigators Principal Investigator: Karen Elkind-Hirsch, Ph.D. Woman's HospitalPrincipal Investigator: Martha Paterson, M.D. Woman's Hospital
Verification DateDecember 2013

Locations[ + expand ][ + ]

Woman's Hospital
Baton Rouge, Louisiana, United States, 70817
Principal Investigator: Karen Elkind-Hirsch, PhD
Recruiting