Type 2 Diabetes
Conditions
Keywords
EPC, diabetes, DPP IV inhibitors
Brief summary
The purpose of this study is to evaluate the effect of Dipeptidyl peptidase (DPP) -IV inhibitor Vildagliptin vs. Glibenclamide on circulating endothelial progenitor cells (EPCs) number in type 2 diabetes patients in metformin failure. Subjects will be followed for 12 months after randomization.
Detailed description
Diabetic patients show a higher cardiovascular risk compared with non-diabetic patients. It is therefore crucial that blood glucose lowering drugs reveal a favorable cardiovascular risk profile independently of metabolic control. EPCs are a subset of circulating mononuclear cells derived from the bone marrow. EPCs play a fundamental role in the formation of new blood vessels (neo-endothelization) and repairing of existing blood vessels (re-endothelization) in order to maintain endothelial homeostasis and integrity. Endothelial damage and tissue ischemia, through the release of growth factors and cytokines, represent a strong stimulus for the mobilization of EPCs from the bone marrow. Reduced EPC number has been related to the presence of traditional risk factors for cardiovascular disease and to the development of atherosclerosis and has been shown to predict cardiovascular (CV)risk. Type 2 diabetes is known to be associated with an increased CV risk and a reduced EPC number. Recent data suggest that DPP-IV inhibitors might be involved in the mechanisms promoting bone-marrow EPC mobilization. This putative ancillary effect of DPP-IV might have a favorable impact on type 2 diabetes, a condition characterized by an increased CV risk. This is a randomized, open-label, active-treatment-controlled, two parallel arm (2:1), intervention trial comparing DPP-IV inhibitor Vildagliptin (100 mg daily) with Glibenclamide (maximum daily dose of 10 mg). Treatment allocation and titration regimens are not blinded. Primary end-point:Absolute change in the EPC number at visit: V0 (randomization), V2 (month 4), V3 (month 8) and V4 (month 12). Secondary end-point: Absolute change in HbA1C compared to baseline.
Interventions
DRUGVildagliptin
100 mg daily
DRUGGlibenclamide
2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day.
DRUGMetformin
concomitant therapy with metformin is present in each arm (MAX dose: 2500 mg/die)
Sponsors
Azienda Ospedaliero-Universitaria di Parma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age equal or above 35 years; * Diagnosis of type 2 diabetes mellitus as defined by the American Diabetes Association , with at least one year of disease duration at the time of the screening visit; * Blood glucose lowering treatment with Metformin alone (monotherapy) at a stable dose of at least 1.5 g/day (or maximum tolerated dose) in the 3 months prior to the screening visit; * Insufficient metabolic control as defined by recent (last six months) HbA1c ≥ 7% in any peripheral laboratory and confirmed at the time of the screening; * Absence of a recent clinically-relevant progression of micro- and macro-vascular complications (see
Exclusion criteria
); * Written informed consent to participate to the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in the Endothelial Progenitor Cell (EPC) Number | V0, V2 (month 4), V4 (12 month) | The study primary endpoint was the change from baseline values of the EPC number in the Vildagliptin vs Glibenclamide arm at 4 and 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in HbA1C Compared to Baseline | V0 (randomization), V2 (month4), V4 (month 12). | The secondary endpoint was the change from baseline values of HbA1C in the Vildagliptin vs Glibenclamide arm at 4 and 12 months |
Countries
Italy
Participant flow
Recruitment details
Individuals with type 2 diabetes were recruited in the outpatient Diabetes Unit of Parma University Hospital
Participants by arm
| Arm | Count |
|---|---|
| Vildagliptin & Metformin Vildagliptin 100 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration
Vildagliptin: 100 mg daily | 40 |
| Glibenclamide & Metformin Glibenclamide maximum dose of 10 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration
Glibenclamide: 2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day. | 24 |
| Total | 64 |
Baseline characteristics
| Characteristic | Vildagliptin & Metformin | Glibenclamide & Metformin | Total |
|---|---|---|---|
| Age, Continuous | 61 years STANDARD_DEVIATION 9 | 63 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 9 |
| Body Mass Index | 29.1 kg/m^2 | 28.9 kg/m^2 | 29.0 kg/m^2 |
| Endothelial Progenitor Cells Number | 39 EPC/10^6 cells | 37.5 EPC/10^6 cells | 38 EPC/10^6 cells |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 24 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HBA1C | 7.7 % | 7.7 % | 7.7 % |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 24 Participants | 64 Participants |
| Region of Enrollment Italy | 40 participants | 24 participants | 64 participants |
| Sex: Female, Male Female | 14 Participants | 7 Participants | 21 Participants |
| Sex: Female, Male Male | 26 Participants | 17 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 5 / 24 |
| serious Total, serious adverse events | 0 / 40 | 0 / 24 |
Outcome results
Primary
Absolute Change in the Endothelial Progenitor Cell (EPC) Number
The study primary endpoint was the change from baseline values of the EPC number in the Vildagliptin vs Glibenclamide arm at 4 and 12 months.
Time frame: V0, V2 (month 4), V4 (12 month)
Population: Intention to treat (ITT) analysis
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vildagliptin & Metformin | Absolute Change in the Endothelial Progenitor Cell (EPC) Number | V2 (4 month) | 37 EPC/10^6 cells |
| Vildagliptin & Metformin | Absolute Change in the Endothelial Progenitor Cell (EPC) Number | V4 (12 month) | 45 EPC/10^6 cells |
| Glibenclamide & Metformin | Absolute Change in the Endothelial Progenitor Cell (EPC) Number | V2 (4 month) | 36 EPC/10^6 cells |
| Glibenclamide & Metformin | Absolute Change in the Endothelial Progenitor Cell (EPC) Number | V4 (12 month) | 32 EPC/10^6 cells |
p-value: <0.05Regression, Linear
p-value: <0.0595% CI: [0.028, 0.695]ANOVA
Secondary
Absolute Change in HbA1C Compared to Baseline
The secondary endpoint was the change from baseline values of HbA1C in the Vildagliptin vs Glibenclamide arm at 4 and 12 months
Time frame: V0 (randomization), V2 (month4), V4 (month 12).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vildagliptin & Metformin | Absolute Change in HbA1C Compared to Baseline | V2 (4 month) | 6.8 percentage |
| Vildagliptin & Metformin | Absolute Change in HbA1C Compared to Baseline | V4 (12 month) | 7.0 percentage |
| Glibenclamide & Metformin | Absolute Change in HbA1C Compared to Baseline | V2 (4 month) | 6.8 percentage |
| Glibenclamide & Metformin | Absolute Change in HbA1C Compared to Baseline | V4 (12 month) | 7.1 percentage |
p-value: <0.0595% CI: [-0.358, 0.224]ANOVA