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. |
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Condition | Disorder of Glucose Regulation |
Intervention | Drug: Sitagliptin-Metformin Drug: Metformin Drug: Placebo pill |
Phase | Phase 4 |
Sponsor | BC Women's Hospital & Health Centre |
Responsible Party | BC Women's Hospital & Health Centre |
ClinicalTrials.gov Identifier | NCT01856907 |
First Received | May 14, 2013 |
Last Updated | December 18, 2013 |
Last verified | December 2013 |
Tracking Information[ + expand ][ + ]
First Received Date | May 14, 2013 |
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Last Updated Date | December 18, 2013 |
Start Date | September 2013 |
Estimated Primary Completion Date | December 2014 |
Current Primary Outcome Measures |
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Current Secondary Outcome Measures | Cardiometabolic 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 Title | Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM |
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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 |
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 Type | Interventional |
Study Phase | Phase 4 |
Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment |
Condition | Disorder of Glucose Regulation |
Intervention | Drug: 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) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 36 |
Estimated Completion Date | December 2014 |
Estimated Primary Completion Date | August 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) |
Gender | Female |
Ages | 18 Years |
Accepts Healthy Volunteers | No |
Contacts | Contact: Karen Elkind-Hirsch, Ph.D. 225-231-5278 karen.elkind-hirsch@womans.org |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01856907 |
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Other Study ID Numbers | RP13-009 |
Has Data Monitoring Committee | Yes |
Information Provided By | BC Women's Hospital & Health Centre |
Study Sponsor | BC Women's Hospital & Health Centre |
Collaborators | Merck Sharp & Dohme Corp. |
Investigators | Principal Investigator: Karen Elkind-Hirsch, Ph.D. Woman's HospitalPrincipal Investigator: Martha Paterson, M.D. Woman's Hospital |
Verification Date | December 2013 |
Locations[ + expand ][ + ]
Woman's Hospital | Baton Rouge, Louisiana, United States, 70817 Principal Investigator: Karen Elkind-Hirsch, PhDRecruiting |
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