Diabetes Mellitus, Type 2
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study was to investigate the mortality and macrovascular morbidity as well as the incidence of malignancies over time, in high-risk diabetic participants who previously received long-term treatment with either pioglitazone or placebo in combination with their usual medication for glycaemic management.
Detailed description
This was a European,multicenter,observational study of participants who were previously treated with pioglitazone or placebo in addition to their existing anti diabetic medication. This 10-year observational study was conducted as a follow-up of PROactive study (NCT00174993) to investigate the CV and macrovascular effects observed with pioglitazone over time during PROactive.In this study,high risk T2DM patients previously enrolled in PROactive were analyzed for long-term incidence,nature, and pattern of all malignancies in pioglitazone and placebo-treated groups.This study enrolled 3599 participants.No treatment was prescribed by this protocol and participants will be managed in accordance with normal medical practice.The planned total duration of the study was 10 years,with data being analyzed and reported every 2 years.Participants were assessed at nominal visits every 6 months and every effort was made to obtain as much of the required information as possible.
Interventions
OTHERNo Intervention
Participants who previously received Pioglitazone in the PROactive study (NCT00174993).
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
36 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Completion of the final visit of the PROactive Study (NCT00174993). * Willingness and ability to give written informed consent for the observational study.
Exclusion criteria
* There were no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With First Occurrence of Macro-vascular Event or Death | Up to Year 10 | The composite macro-vascular event or death included all-cause mortality, non-fatal myocardial infarction, cardiac intervention, stroke, major leg amputation (above the ankle), bypass surgery or revascularization in the leg. The percentage of participants in the observational study population having first occurrence of macro-vascular event or death during the 10-year observational study period was analyzed. The data were analyzed using the Cox regression with respect to time to the first occurrence of macro-vascular event or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidences With Malignancies | Up to Year 10 | Percentage of participants with incidences of at least 1 malignancy was reported. All malignancies included adrenal, biliary, bladder, brain, breast, cervix, colon/rectal, gastric, hematological, hepatic, lung, mesothelioma, metastases, oesophageal, oropharyngeal, ovarian/uterine, pancreas, prostate, renal, skin and others. |
Participant flow
Recruitment details
Participants took part at 228 sites in 18 European countries including Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Latvia, Lithuania, Netherlands, Norway, Poland, Slovakia, Sweden, Switzerland, and the United Kingdom from 02 November 2004 to 10 March 2015.
Pre-assignment details
Participants with a historical diagnosis of Type 2 diabetes mellitus (T2DM) who were previously treated with pioglitazone or placebo in the PROactive study (NCT00174993) were enrolled in this observational study according to their originally assigned treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Participants who were previously treated with pioglitazone 15, 30, or 45 milligram tablets, orally, once daily during the PROactive study (NCT00174993) were followed up to 10 years in this observational study. | 1,820 |
| Placebo Participants who were previously treated with placebo-matching pioglitazone tablets, orally, once daily during the PROactive (NCT00174993) study were followed up to 10 years. | 1,779 |
| Total | 3,599 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 619 | 649 |
| Overall Study | Lost to Follow-up | 171 | 151 |
| Overall Study | Unconfirmed for lost to follow-up | 85 | 67 |
| Overall Study | Withdrawal by Subject | 13 | 5 |
Baseline characteristics
| Characteristic | Pioglitazone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 7.51 | 61.4 years STANDARD_DEVIATION 7.8 | 61.6 years STANDARD_DEVIATION 7.66 |
| Body mass index (BMI) | 30.834 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.7978 | 31.078 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.7135 | 30.955 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.7572 |
| Duration of T2DM | 9.3 Years STANDARD_DEVIATION 6.81 | 9.3 Years STANDARD_DEVIATION 6.96 | 9.3 Years STANDARD_DEVIATION 6.88 |
| Race/Ethnicity, Customized Asian/Oriental | 18 Participants | 14 Participants | 32 Participants |
| Race/Ethnicity, Customized Black | 7 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 1794 Participants | 1760 Participants | 3554 Participants |
| Region of Enrollment Austria | 45 Participants | 47 Participants | 92 Participants |
| Region of Enrollment Belgium | 21 Participants | 18 Participants | 39 Participants |
| Region of Enrollment Czech Republic | 40 Participants | 40 Participants | 80 Participants |
| Region of Enrollment Denmark | 32 Participants | 27 Participants | 59 Participants |
| Region of Enrollment Estonia | 50 Participants | 53 Participants | 103 Participants |
| Region of Enrollment Finland | 138 Participants | 124 Participants | 262 Participants |
| Region of Enrollment France | 28 Participants | 30 Participants | 58 Participants |
| Region of Enrollment Germany | 104 Participants | 104 Participants | 208 Participants |
| Region of Enrollment Hungary | 356 Participants | 360 Participants | 716 Participants |
| Region of Enrollment Latvia | 178 Participants | 175 Participants | 353 Participants |
| Region of Enrollment Lithuania | 120 Participants | 115 Participants | 235 Participants |
| Region of Enrollment Netherlands | 16 Participants | 18 Participants | 34 Participants |
| Region of Enrollment Norway | 44 Participants | 47 Participants | 91 Participants |
| Region of Enrollment Poland | 374 Participants | 366 Participants | 740 Participants |
| Region of Enrollment Slovakia | 39 Participants | 42 Participants | 81 Participants |
| Region of Enrollment Sweden | 56 Participants | 58 Participants | 114 Participants |
| Region of Enrollment Switzerland | 11 Participants | 7 Participants | 18 Participants |
| Region of Enrollment United Kingdom | 168 Participants | 148 Participants | 316 Participants |
| Sex: Female, Male Female | 632 Participants | 626 Participants | 1258 Participants |
| Sex: Female, Male Male | 1188 Participants | 1153 Participants | 2341 Participants |
| Weight | 87.72 Kilograms (kg) STANDARD_DEVIATION 15.607 | 88.62 Kilograms (kg) STANDARD_DEVIATION 15.451 | 88.17 Kilograms (kg) STANDARD_DEVIATION 15.534 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Percentage of Participants With First Occurrence of Macro-vascular Event or Death
The composite macro-vascular event or death included all-cause mortality, non-fatal myocardial infarction, cardiac intervention, stroke, major leg amputation (above the ankle), bypass surgery or revascularization in the leg. The percentage of participants in the observational study population having first occurrence of macro-vascular event or death during the 10-year observational study period was analyzed. The data were analyzed using the Cox regression with respect to time to the first occurrence of macro-vascular event or death.
Time frame: Up to Year 10
Population: The observational study population consisted of participants who enrolled in this study after completing the final visit of PROactive study (NCT00174993).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone | Percentage of Participants With First Occurrence of Macro-vascular Event or Death | 58 percentage of participants |
| Placebo | Percentage of Participants With First Occurrence of Macro-vascular Event or Death | 60.3 percentage of participants |
Comparison: Test for statistical difference between pioglitazone and placebo with respect to time of first occurrence of the primary composite outcome event.p-value: 0.344495% CI: [0.88, 1.04]Regression, Cox
Secondary
Incidences With Malignancies
Percentage of participants with incidences of at least 1 malignancy was reported. All malignancies included adrenal, biliary, bladder, brain, breast, cervix, colon/rectal, gastric, hematological, hepatic, lung, mesothelioma, metastases, oesophageal, oropharyngeal, ovarian/uterine, pancreas, prostate, renal, skin and others.
Time frame: Up to Year 10
Population: The observational study population consisted of participants who enrolled in this study after completing the final visit of PROactive study (NCT00174993).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone | Incidences With Malignancies | 12.9 percentage of participants |
| Placebo | Incidences With Malignancies | 13.2 percentage of participants |
Comparison: Test for statistical difference between pioglitazone and placebo with respect to time of first occurrence of the primary composite outcome event.95% CI: [0.83, 1.16]