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

Disorder of Glucose Regulation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01856907
• Other study ID #: RP13-009
• Status: Completed
• Phase: Phase 4
• First received: May 14, 2013
• Last updated: January 19, 2018
• Start date: September 28, 2013
• Est. completion date: September 28, 2017

Study information

• Verified date: January 2018
• Source: Woman's
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: September 28, 2017
• Est. primary completion date: September 5, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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)

Related Conditions & MeSH terms

• Disorder of Glucose Regulation

Intervention

Drug:
• Sitagliptin-Metformin
Experimental -dipeptidyl peptidase-4 (DPP-4) inhibitor- oral medication
• Metformin
Biguanide- insulin sensitizer
• Placebo pill
Will evaluate effect of lifestyle and diet only

Locations

Country	Name	City	State
United States	Woman's Hospital	Baton Rouge	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Woman's	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Liver Enzymes as Safety Measure	Number of patients with no clinically significant changes in liver enzymes-measure of liver enzymes was a study safety endpoint	16 weeks
Primary	Normalization of Glucose Levels	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	16 weeks
Secondary	Fasting Blood Glucose	Blood glucose in the fasting state	16 weeks
Secondary	Mean Blood Glucose Level From the Oral Glucose Tolerance Test (OGTT)	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..	16 weeks
Secondary	Fasting Insulin Resistance	Insulin resistance calculated from fasting glucose and insulin levels known as HOMA-IR	16 weeks
Secondary	Matsuda Index of Insulin Sensitivity	Composite insulin sensitivity index calculated from from glucose and insulin levels obtained during the OGTT	16 weeks
Secondary	Oral Disposition Index	Measure of pancreatic beta cell compensatory action known as IS-SI	16 weeks
Secondary	Triglyceride/HDL-Cholesterol Ratio	The ratio of triglyceride to HDL cholesterol is used as an indirect measure of insulin resistance	16 weeks
Secondary	Body Mass Index	Measure of body weight corrected by height	16 weeks
Secondary	Waist Circumference	Measure of central fat	16 weeks
Secondary	Waist-to-Height Ratio	Measure of central obesity adjusted for stature	16 weeks