Pioglitazone Versus Metformin in Type 2 Diabetes

Overview[ - collapse ][ - ]

Purpose Type 2 diabetes is an epidemic. Its long-term consequences translate into enormous human suffering and economic costs; however, much of the morbidity associated with long-term microvascular and neuropathic complications can be substantially reduced by interventions that achieve glucose levels close to the nondiabetic range. However, none of the recent intervention studies has demonstrated a benefit of intensive glycemic control on their primary CVD outcomes. The investigators report the findings of a long-term randomized and comparator-controlled clinical trial conducted in patients with newly-diagnosed type 2 diabetes. The investigators compared the effect of pioglitazone with that of metformin on circulating endothelial cell-derived submicroscopic membranous vesicles, termed microparticles: because of their putative role in inflammatory processes and their ability to directly affect endothelial functions, they are gaining increasing popularity as a surrogate marker of cardiovascular outlook. Metformin was chosen as a comparator because the American Diabetes Association recommendations suggest to start therapy in newly-diagnosed type 2 diabetic subjects combining a drug (metformin) with lifestyle changes. Moreover, the mechanism of action of pioglitazone is distinct from that of metformin.
ConditionType 2 Diabetes
InterventionDrug: Pioglitazone
Drug: Metformin
PhasePhase 4
SponsorSecond University of Naples
Responsible PartySecond University of Naples
ClinicalTrials.gov IdentifierNCT00815399
First ReceivedDecember 29, 2008
Last UpdatedDecember 29, 2008
Last verifiedSeptember 2008

Tracking Information[ + expand ][ + ]

First Received DateDecember 29, 2008
Last Updated DateDecember 29, 2008
Start DateOctober 2007
Estimated Primary Completion DateApril 2009
Current Primary Outcome MeasuresCirculating Endothelial microparticles [Time Frame: six months] [Designated as safety issue: Yes]
Current Secondary Outcome MeasuresGlucose profile, lipid profile, hemoglobin A1c, carotid intima-media thickness [Time Frame: six months] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitlePioglitazone Versus Metformin in Type 2 Diabetes
Official TitleEffect of Pioglitazone Compared With Metformin on Endothelial Microparticles in Type 2 Diabetes. A Randomized Trial
Brief Summary
Type 2 diabetes is an epidemic. Its long-term consequences translate into enormous human
suffering and economic costs; however, much of the morbidity associated with long-term
microvascular and neuropathic complications can be substantially reduced by interventions
that achieve glucose levels close to the nondiabetic range. However, none of the recent
intervention studies has demonstrated a benefit of intensive glycemic control on their
primary CVD outcomes.

The investigators report the findings of a long-term randomized and comparator-controlled
clinical trial conducted in patients with newly-diagnosed type 2 diabetes. The investigators
compared the effect of pioglitazone with that of metformin on circulating endothelial
cell-derived submicroscopic membranous vesicles, termed microparticles: because of their
putative role in inflammatory processes and their ability to directly affect endothelial
functions, they are gaining increasing popularity as a surrogate marker of cardiovascular
outlook. Metformin was chosen as a comparator because the American Diabetes Association
recommendations suggest to start therapy in newly-diagnosed type 2 diabetic subjects
combining a drug (metformin) with lifestyle changes. Moreover, the mechanism of action of
pioglitazone is distinct from that of metformin.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
ConditionType 2 Diabetes
InterventionDrug: Pioglitazone
15-45 mg/die
Drug: Metformin
500-2000 mg/die
Study Arm (s)
  • Experimental: 1
  • Active Comparator: 2

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment150
Estimated Completion DateApril 2009
Estimated Primary Completion DateMarch 2009
Eligibility Criteria
Inclusion Criteria:

- Men and women aged 30-75 years, with newly-diagnosed type 2 diabetes (according to
the ADA criteria) and never treated with antihyperglycemic drugs, were selected for
the study. Inclusion criteria also included a body mass index (BMI) >25 kg/m2, and
HbA1c level <10%.

Exclusion Criteria:

- Pregnancy or breast-feeding

- Any investigational drug within the previous 3 months

- Use of agents affecting glycemic control (systemic glucocorticoids, and weight-loss
drugs)

- Presence of any clinically relevant somatic or mental diseases that anticipated poor
adherence to diet regimens

- To minimize the likelihood of including subjects with late-onset type 1 diabetes,
candidates with a positive test for anti-GAD antibody or with fasting plasma
C-peptide less than 0.76 ng/L (<0.25 pmol/L) were excluded

- Also excluded were patients with abnormal laboratory tests, including liver enzymes
(alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) greater
than 3 times the upper limit of normal, and serum creatinine greater than 123.8
μmol/L (1.4 mg/dL).
GenderBoth
Ages30 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesItaly

Administrative Information[ + expand ][ + ]

NCT Number NCT00815399
Other Study ID NumbersDMD/2007/10
Has Data Monitoring CommitteeNo
Information Provided BySecond University of Naples
Study SponsorSecond University of Naples
CollaboratorsNot Provided
Investigators Not Provided
Verification DateSeptember 2008

Locations[ + expand ][ + ]

Department of Geriatrics and Metabolic Diseases
Naples, Italy, 80138