Metformin and Sitagliptin in Women With Previous Gestational Diabetes

Effects of Treatment With Metformin and/or Sitagliptin on Beta-cell Function and Insulin Resistance in Women With Previous Gestational Diabetes

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.

Study Overview

• Status: Completed
• Conditions: Pre-diabetes
• Intervention / Treatment: Drug: Metformin; Drug: Sitagliptin; Drug: Sitagliptin + Metformin

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
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Pisa, Italy, 56124
    • Department of Endocrinology and Metabolism, University of Pisa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Metformin; Metformin 850 mg bid	Drug: Metformin; Metformin 850 mg bid; Other Names: Glucophage
ACTIVE_COMPARATOR: Sitagliptin; Sitagliptin 100 mg qd	Drug: Sitagliptin; Sitagliptin 100 mg qd; Other Names: januvia
ACTIVE_COMPARATOR: Sitagliptin+Metformin; Sitagliptin 100 mg qd plus Metformin 850 mg bid	Drug: Sitagliptin + Metformin; sitagliptin 100mg + metformin 850mg; Other Names: janumet

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	Sitagliptin and/or metformin effects on insulin resistance, evaluated by clamp, HOMA-index and ISI-Method..	4 months
Glucose control	Sitagliptin and/or metformin effects on glucose control evaluated by OGTT and HbA1c levels.	4 months

Collaborators and Investigators

• Sponsor: University of Pisa
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): December 1, 2018

Study Registration Dates

• First Submitted: April 13, 2011
• First Submitted That Met QC Criteria: April 13, 2011
• First Posted (ESTIMATE): April 15, 2011

Study Record Updates

• Last Update Posted (ACTUAL): March 25, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: insulin resistance; beta-cell function
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Prediabetic State; Diabetes, Gestational; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: SITA-previousGDM