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

NCT ID: NCT01856907

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-28
• Study Completion Date: 2017-09-28

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.

Conditions

Disorder of Glucose Regulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Sitagliptin-Metformin

50 mg/1000 mg twice a day (BID)

Group Type: EXPERIMENTAL

Sitagliptin-Metformin

Intervention Type: DRUG

Experimental -dipeptidyl peptidase-4 (DPP-4) inhibitor- oral medication

Placebo pill

1 pill/BID for 16 weeks

Group Type: PLACEBO_COMPARATOR

Placebo pill

Intervention Type: DRUG

Will evaluate effect of lifestyle and diet only

Metformin

1000 mg BID

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Biguanide- insulin sensitizer

Interventions

Sitagliptin-Metformin

Experimental -dipeptidyl peptidase-4 (DPP-4) inhibitor- oral medication

Intervention Type: DRUG

Metformin

Biguanide- insulin sensitizer

Intervention Type: DRUG

Placebo pill

Will evaluate effect of lifestyle and diet only

Intervention Type: DRUG

Other Intervention Names

Janumet; Glucophage; placebo control

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Woman's

OTHER

Sponsor Role: lead

Responsible Party

Karen Elkind-Hirsch

Director of Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karen Elkind-Hirsch, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Woman's Hospital, Louisiana

Martha Paterson, M.D.

Role: PRINCIPAL_INVESTIGATOR

Woman's Hospital, Louisiana

Locations

Woman's Hospital

Baton Rouge, Louisiana, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

RP13-009

Identifier Type: -

Identifier Source: org_study_id