Metformin and Sitagliptin in Women With Previous Gestational Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01336322
Recruitment Status : Recruiting
First Posted : April 15, 2011
Last Update Posted : January 17, 2018
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Prof. Stefano Del Prato, University of Pisa

Brief Summary:
The goal of the present research is to compare the effects of treatment with metformin and sitagliptin, alone or in association, in women with previous gestational diabetes to evaluate the impact of the two drugs on beta-cell function. The study results may contribute to give a rational approach for future investigations.

Condition or disease Intervention/treatment Phase
Pre-diabetes Drug: Metformin Drug: Sitagliptin Drug: Sitagliptin + Metformin Phase 2

Detailed Description:

A randomized, double blinded study, on 45 women with previous gestational diabetes and impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) to assess the effects of a 4-month treatment with metformin and/or a dipeptidyl peptidase-4 inhibitor (sitagliptin) on beta-cell function and insulin resistance.

At baseline, all women will have a standardized medical history, physical, and laboratory examination. Plasma glucose, insulin, pro-insulin, C-peptide, glucagon, adipokines, pro-inflammatory molecules, and lipid profile will be determined in fasting condition. A 75g OGTT will be performed after an overnight fasting and sample will be drawn at 15, 30, 60, 90 and 120 minutes for plasma glucose, C-peptide, glucagon and GLP-1 determinations. Women with IFG or IGT will be recruited and undergo to a hyperglycemic clamp with arginin bolus at the end of the test. Then the women will be randomized in 3 treatment groups: metformin (850 mg bid), sitagliptin (100 mg qd)or metformin (850 mg bid) + sitagliptin (100 mg qd). After 4-month treatment, the baseline evaluation will be repeated.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Treatment With Metformin and/or Sitagliptin on Beta-cell Function and Insulin Resistance in Women With Previous Gestational Diabetes
Study Start Date : May 2011
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Metformin
Metformin 850 mg bid
Drug: Metformin
Metformin 850 mg bid
Other Name: Glucophage

Active Comparator: Sitagliptin
Sitagliptin 100 mg qd
Drug: Sitagliptin
Sitagliptin 100 mg qd
Other Name: januvia

Active Comparator: Sitagliptin+Metformin
Sitagliptin 100 mg qd plus Metformin 850 mg bid
Drug: Sitagliptin + Metformin
sitagliptin 100mg + metformin 850mg
Other Name: janumet

Primary Outcome Measures :
  1. Beta-cell function [ Time Frame: 4 months ]
    Sitagliptin and/or metformin effects on beta-cell function (ISR = Insulin Secretion Rate) evaluated by mathematical model by Mari A. (Am J Physiology 2002)

Secondary Outcome Measures :
  1. Insulin resistance [ Time Frame: 4 months ]
    Sitagliptin and/or metformin effects on insulin resistance, evaluated by clamp, HOMA-index and ISI-Method..

  2. Glucose control [ Time Frame: 4 months ]
    Sitagliptin and/or metformin effects on glucose control evaluated by OGTT and HbA1c levels.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Female subjects aged ≥18 and ≤45 years
  • Caucasian race
  • History of previous gestational diabetes (in the screening) during pregnancy.
  • Female of childbearing potential must use effective contraceptive measures for at last 1 month prior to entry into the study and should continue to use the some contraceptive method during the overall study period
  • Written informed consent obtained

Exclusion Criteria:

  • Patients diagnosed with type 1 insulin dependent diabetes
  • Diagnosis of diabetes in the 75g OGTT performed at entry
  • BMI ≤18 or ≥50 Kg/m2
  • Chronic impaired renal function
  • Impaired liver function as shown by transaminase levels ≥ twice above the upper normal range
  • History of hypersensitivity to metformin
  • Pregnant or breast-feeding women, or women planning to become pregnant during the study
  • Failure to use adequate contraception (Women of current reproductive only)
  • Mental condition rending the subject unable to understand the nature, scope and possible consequences of the study
  • Any clinically significant major organ system disease
  • Patients with underlying concomitant medication requiring a long-term use of drugs potentially acting on glucose metabolism (e.g. corticosteroids, diuretics, beta-adrenergic drugs or others)
  • Treatment or likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
  • History of drug or alcohol abuse within the last 2 years or current addiction to substances of abuse
  • Any disease or condition that in the opinion of the investigator may interfere with the completion of the study
  • Subjects unlikely to comply with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01336322

Contact: Stefano Del Prato, MD +39 050 995103
Contact: Alessandra Bertolotto, MD

Department of Endocrinology and Metabolism, University of Pisa Recruiting
Pisa, Italy, 56124
Contact: Stefano Del Prato, MD    +39 050 995103   
Sub-Investigator: Graziano Di Cianni, MD         
Sponsors and Collaborators
University of Pisa
Merck Sharp & Dohme Corp.
Principal Investigator: Stefano Del Prato, MD University of Pisa

Responsible Party: Prof. Stefano Del Prato, Clinical Resercher, University of Pisa Identifier: NCT01336322     History of Changes
Other Study ID Numbers: SITA-previousGDM
First Posted: April 15, 2011    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: April 2017

Keywords provided by Prof. Stefano Del Prato, University of Pisa:
beta-cell function
insulin resistance

Additional relevant MeSH terms:
Diabetes Mellitus
Insulin Resistance
Diabetes, Gestational
Prediabetic State
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pregnancy Complications
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action