Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM
Information source: Woman's
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Disorder of Glucose Regulation
Intervention: Sitagliptin-Metformin (Drug); Metformin (Drug); Placebo pill (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Woman's Official(s) and/or principal investigator(s): Karen Elkind-Hirsch, Ph.D., Principal Investigator, Affiliation: Woman's Hospital, Louisiana Martha Paterson, M.D., Principal Investigator, Affiliation: Woman's Hospital, Louisiana
Overall contact: Karen Elkind-Hirsch, Ph.D., Phone: 225-231-5278, Email: karen.elkind-hirsch@womans.org
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
Primary outcome: ß-cell compensatory functionSurrogate measures of insulin sensitivity and secretion Fasting and 2 hour glucose levels after glucose load
Secondary outcome: Cardiometabolic risk factors
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 42 Years.
Gender(s): Female.
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)
Locations and Contacts
Karen Elkind-Hirsch, Ph.D., Phone: 225-231-5278, Email: karen.elkind-hirsch@womans.org
Woman's Hospital, Baton Rouge, Louisiana 70817, United States; Recruiting Karen Elkind-Hirsch, PhD, Principal Investigator Martha Paterson, MD, Sub-Investigator
Additional Information
Starting date: September 2013
Last updated: June 1, 2015
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