Clinical trial NCT00815399: Pioglitazone Versus Metformin in Type 2 Diabetes
Official title: Effect of Pioglitazone Compared With Metformin on Endothelial Microparticles in Type 2 Diabetes. A Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
First posted: 2008-12-30
Enrollment: 150
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Circulating Endothelial microparticles
timeFrame: six months
Secondary outcomes:
measure: Glucose profile, lipid profile, hemoglobin A1c, carotid intima-media thickness
timeFrame: six months
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Department of Geriatrics and Metabolic Diseases
Study officials:
References:
citation: Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, D'Agostino RB Sr, Perez A, Provost JC, Haffner SM. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006 Dec 6;296(21):2572-81. doi: 10.1001/jama.296.21.joc60158. Epub 2006 Nov 13.