Metformin and Sitagliptin in Women With Previous Gestational Diabetes

• ClinicalTrials.gov Identifier: NCT01336322
• Recruitment Status: Completed
• First Posted: April 15, 2011
• Last Update Posted: March 25, 2019
• Sponsor: University of Pisa
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Prof. Stefano Del Prato, University of Pisa

Study Description

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 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
• Actual Primary Completion Date: December 2017
• Actual Study Completion Date: December 2018

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Italy

Department of Endocrinology and Metabolism, University of Pisa

Pisa, Italy, 56124

Sponsors and Collaborators

University of Pisa

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Stefano Del Prato, MD; University of Pisa

More Information

• Responsible Party: Prof. Stefano Del Prato, Clinical Resercher, University of Pisa
• ClinicalTrials.gov Identifier: NCT01336322
• Other Study ID Numbers: SITA-previousGDM
• First Posted: April 15, 2011
• Last Update Posted: March 25, 2019
• Last Verified: March 2019

Keywords provided by Prof. Stefano Del Prato, University of Pisa:

beta-cell function; insulin resistance

Additional relevant MeSH terms:

Diabetes, Gestational; Diabetes Mellitus; Prediabetic State; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Metformin; Sitagliptin Phosphate; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action