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

NCT01856907 | Completed Phase 4 Results DMC

• 1 other identifier: RP13-009
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Disorder of Glucose Regulation

Keywords

prediabetes; impaired fasting/impaired glucose tolerance; post gestational diabetes; diabetes prevention

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Fasting Blood Glucose

  16 weeks

• Mean Blood Glucose Level From the Oral Glucose Tolerance Test (OGTT)

  16 weeks

• Fasting Insulin Resistance

  16 weeks

• Matsuda Index of Insulin Sensitivity

  16 weeks

• Oral Disposition Index

  16 weeks

Other Outcomes (1)

• Liver Enzymes as Safety Measure

  16 weeks

Study Arms (3)

Sitagliptin-Metformin

EXPERIMENTAL

50 mg/1000 mg twice a day (BID)

Drug: Sitagliptin-Metformin

Placebo pill

PLACEBO COMPARATOR

1 pill/BID for 16 weeks

Drug: Placebo pill

Metformin

ACTIVE COMPARATOR

1000 mg BID

Drug: Metformin

Interventions

Sitagliptin-Metformin DRUG

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

Also known as: Janumet

Sitagliptin-Metformin

Metformin DRUG

Biguanide- insulin sensitizer

Also known as: Glucophage

Metformin

Placebo pill DRUG

Will evaluate effect of lifestyle and diet only

Also known as: placebo control

Placebo pill

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Woman's: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Woman's Hospital

Baton Rouge, Louisiana, 70817, United States

Location

MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance

Interventions

Sitagliptin Phosphate, Metformin Hydrochloride Drug Combination; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Sitagliptin Phosphate; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

Important limitations of the present study were the small number of patients in the treatment groups and the short interval (16 weeks) of drug treatment. Second, surrogate measures were used to estimate insulin sensitivity and secretion.

Results Point of Contact

• Title: Dr Karen Elkind-Hirsch
• Organization: Woman's Hospital

karen.elkind-hirsch@womans.org

225-231-5278

Study Officials

• Karen Elkind-Hirsch, Ph.D.

  Woman's Hospital, Louisiana

  PRINCIPAL INVESTIGATOR

• Martha Paterson, M.D.

  Woman's Hospital, Louisiana

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 20, 2013
• Study Start: September 28, 2013
• Primary Completion: September 5, 2017
• Study Completion: September 28, 2017
• Last Updated: January 23, 2018
• Results First Posted: January 23, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)