Trial Outcomes & Findings for Efficacy Study of Pioglitazone and Metformin and Association Between Pioglitazone Response and Peroxisome Proliferator-activated Receptor Gamma Gene Variants in Bangladeshi Type 2 Diabetes Mellitus Subjects (NCT NCT01589445)
NCT ID: NCT01589445
Last Updated: 2014-02-28
Results Overview
Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.
COMPLETED
PHASE4
77 participants
3 months for each drug
2014-02-28
Participant Flow
Location: Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM),Dhaka, Bangladesh and National Forensic DNA Profiling Laboratory, Dhaka Medical College, Dhaka. Recruitment of patients were started at November 2008 and ended at December 2010.
130 Type 2 Diabetes Mellitus (T2DM) out door patients of BIRDEM were screened to participate in the study.80 patients signed consent form and 77 enrolled the trial.3 patients didn't participate due to unknown cause.The patients were directed to follow their routine diet chart as before.
Participant milestones
| Measure |
Single Group Study With Two Drugs- Pioglitazone and Metformin
Group 001-Pioglitazone 30 mg tablet once daily Group 002-Metformin 850 mg tablet once daily
The single group study with a wash out period of one month with metformin 850 mg tablet once daily.
77 patients started with pioglitazone(7 drop out)and after one month wash out period 70 patients started with metformin (9 drop out).
48 patients for the 1st 3 months of pioglitazone and 32 patients for the 2nd 3 months of metformin responded to the drugs respectively according to the response rate\[The treatment target was set to reduce at least ≥10% FBG or ≥1% HbA1c in the patients considering as the responder group\].
|
|---|---|
|
001 (Pioglitazone) -3 Months
STARTED
|
77
|
|
001 (Pioglitazone) -3 Months
COMPLETED
|
70
|
|
001 (Pioglitazone) -3 Months
NOT COMPLETED
|
7
|
|
002 (Metformin)-3 Months
STARTED
|
70
|
|
002 (Metformin)-3 Months
COMPLETED
|
61
|
|
002 (Metformin)-3 Months
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
Single Group Study With Two Drugs- Pioglitazone and Metformin
Group 001-Pioglitazone 30 mg tablet once daily Group 002-Metformin 850 mg tablet once daily
The single group study with a wash out period of one month with metformin 850 mg tablet once daily.
77 patients started with pioglitazone(7 drop out)and after one month wash out period 70 patients started with metformin (9 drop out).
48 patients for the 1st 3 months of pioglitazone and 32 patients for the 2nd 3 months of metformin responded to the drugs respectively according to the response rate\[The treatment target was set to reduce at least ≥10% FBG or ≥1% HbA1c in the patients considering as the responder group\].
|
|---|---|
|
001 (Pioglitazone) -3 Months
Protocol Violation
|
1
|
|
001 (Pioglitazone) -3 Months
Withdrawal by Subject
|
1
|
|
001 (Pioglitazone) -3 Months
Lost to Follow-up
|
2
|
|
001 (Pioglitazone) -3 Months
Lack of Efficacy
|
1
|
|
001 (Pioglitazone) -3 Months
biasedness about the double blind method
|
2
|
|
002 (Metformin)-3 Months
Lack of Efficacy
|
1
|
|
002 (Metformin)-3 Months
Lost to Follow-up
|
2
|
|
002 (Metformin)-3 Months
Protocol Violation
|
2
|
|
002 (Metformin)-3 Months
Adverse Event
|
2
|
|
002 (Metformin)-3 Months
Husbands of female patients refrained
|
2
|
Baseline Characteristics
Efficacy Study of Pioglitazone and Metformin and Association Between Pioglitazone Response and Peroxisome Proliferator-activated Receptor Gamma Gene Variants in Bangladeshi Type 2 Diabetes Mellitus Subjects
Baseline characteristics by cohort
| Measure |
Single Group Study With Two Interventions
n=77 Participants
This was double blind, single group and "within subjects" designed study with two interventions.We screened 130 patients, selected 77 subjects who received drug Code 001, then gone through one month wash out period, then received Code 002.For PPARγ genotyping blood samples were collected from patients. There were found two groups-Pro12Pro and Pro12Ala. Baseline evaluation included detailed medical history,socioeconomic status, physical examination, and laboratory investigations for biomedical variables,psychosocial factors according to Patient Health Questionnaire (PHQ-9) and WHO-5 questionnaires.We decoded blinded drug after analyzing the results and knew that pioglitazone (30 mg once daily) was coded as 001 and metformin (850 mg once daily) as code 002.
For statistical analysis we compare Pio vs Met, Pro12Pro vs Pro12Ala, met responder vs non responder.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
77 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
46 years
STANDARD_DEVIATION 6.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
|
Region of Enrollment
Bangladesh
|
77 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 months for each drugPopulation: After completion of both of the treatments, it is found in the 3rd month some patients didn't response according to the response rate and during result analysis the responded numbers (48 and 32)were considered only. That's why the number of participant in both the trials didn't match with number of participants analyzed.
Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.
Outcome measures
| Measure |
Pioglitazone (001 Group)
n=48 Participants
Dose: Pioglitazone tablet 30 mg once daily for 3 months
|
Metformin (002 Group)
n=32 Participants
Dose: Metformin tablet 850 mg once daily for 3 months
|
|---|---|---|
|
Comparison of Changes in Fasting Serum Glucose (FSG)With Pioglitazone and Metformin
Baseline FSG
|
6.9 mmol/l
Standard Deviation 2.5
|
6.2 mmol/l
Standard Deviation 1.6
|
|
Comparison of Changes in Fasting Serum Glucose (FSG)With Pioglitazone and Metformin
3rd Month FSG
|
5.4 mmol/l
Standard Deviation 1.2
|
6.5 mmol/l
Standard Deviation 2.6
|
PRIMARY outcome
Timeframe: 3 months for each drugPopulation: After completion of both of the treatments, it is found in the 3rd month some patients didn't response according to the response rate and during result analysis the responded numbers (48 and 32)were considered only. That's why the number of participant in both the trials didn't match with number of participants analyzed.
Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.
Outcome measures
| Measure |
Pioglitazone (001 Group)
n=48 Participants
Dose: Pioglitazone tablet 30 mg once daily for 3 months
|
Metformin (002 Group)
n=32 Participants
Dose: Metformin tablet 850 mg once daily for 3 months
|
|---|---|---|
|
Comparison of Changes in Glycosylated Hemoglobin (HbA1c)With Pioglitazone and Metformin
Baseline HbA1c
|
7.3 percentage
Standard Deviation 1.2
|
7.8 percentage
Standard Deviation 2.0
|
|
Comparison of Changes in Glycosylated Hemoglobin (HbA1c)With Pioglitazone and Metformin
3rd month HbA1c
|
6.7 percentage
Standard Deviation 1.1
|
7.0 percentage
Standard Deviation 1.5
|
PRIMARY outcome
Timeframe: 3 months for each drugPopulation: After completion of both of the treatments, it is found in the 3rd month some patients didn't response according to the response rate and during result analysis the responded numbers (48 and 32)were considered only. That's why the number of participant in both the trials didn't match with number of participants analyzed.
Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1: Homeostasis Model Assessment Insulin Resistance(HOMA IR) Analysis 2: Quantitative Insulin sensitivity Check Index(QUICKI)
Outcome measures
| Measure |
Pioglitazone (001 Group)
n=48 Participants
Dose: Pioglitazone tablet 30 mg once daily for 3 months
|
Metformin (002 Group)
n=32 Participants
Dose: Metformin tablet 850 mg once daily for 3 months
|
|---|---|---|
|
Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin
Baseline QUICKI
|
0.52 Score on a scale ( SI unit)
Standard Deviation 0.08
|
0.57 Score on a scale ( SI unit)
Standard Deviation 0.12
|
|
Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin
3rd month QUICKI
|
0.59 Score on a scale ( SI unit)
Standard Deviation 0.12
|
0.54 Score on a scale ( SI unit)
Standard Deviation 0.09
|
|
Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin
Baseline HOMA IR
|
5.1 Score on a scale ( SI unit)
Standard Deviation 3.6
|
3.7 Score on a scale ( SI unit)
Standard Deviation 2.9
|
|
Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin
3rd month HOMA IR
|
2.9 Score on a scale ( SI unit)
Standard Deviation 1.9
|
4.3 Score on a scale ( SI unit)
Standard Deviation 3.6
|
PRIMARY outcome
Timeframe: 3 months for each drugPopulation: After completion of both of the treatments, it is found in the 3rd month some patients didn't response according to the response rate and during result analysis the responded numbers (48 and 32)were considered only. That's why the number of participant in both the trials didn't match with number of participants analyzed.
Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1: Homeostatic Model Assessment of Beta cell function(HOMA percent B) Analysis 2: Homeostatic Model Assessment of Insulin Sensitivity (Homa percent S)
Outcome measures
| Measure |
Pioglitazone (001 Group)
n=48 Participants
Dose: Pioglitazone tablet 30 mg once daily for 3 months
|
Metformin (002 Group)
n=32 Participants
Dose: Metformin tablet 850 mg once daily for 3 months
|
|---|---|---|
|
Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin
Baseline HOMA percent sensitivity
|
51.1 percentage
Standard Deviation 30.8
|
76.2 percentage
Standard Deviation 52.0
|
|
Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin
3rd month HOMA percent sensitivity
|
69.3 percentage
Standard Deviation 31.0
|
67.2 percentage
Standard Deviation 45.0
|
|
Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin
Baseline HOMA percent beta cells function
|
118.9 percentage
Standard Deviation 87.0
|
109.3 percentage
Standard Deviation 61.0
|
|
Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin
3rd month HOMA percent beta cells function
|
132.3 percentage
Standard Deviation 66.0
|
116.0 percentage
Standard Deviation 77.0
|
PRIMARY outcome
Timeframe: 3 months for each drugPopulation: After completion of both of the treatments, it is found in the 3rd month some patients didn't response according to the response rate and during result analysis the responded numbers (48 and 32)were considered only. That's why the number of participant in both the trials didn't match with number of participants analyzed.
Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.
Outcome measures
| Measure |
Pioglitazone (001 Group)
n=48 Participants
Dose: Pioglitazone tablet 30 mg once daily for 3 months
|
Metformin (002 Group)
n=32 Participants
Dose: Metformin tablet 850 mg once daily for 3 months
|
|---|---|---|
|
Comparison of Changes in Fasting Serum Insulin (FSI)With Pioglitazone and Metformin
Baseline FSI
|
16.2 μU/ml
Standard Deviation 8.7
|
13.0 μU/ml
Standard Deviation 8.8
|
|
Comparison of Changes in Fasting Serum Insulin (FSI)With Pioglitazone and Metformin
3rd month FSI
|
12.3 μU/ml
Standard Deviation 7.5
|
13.9 μU/ml
Standard Deviation 7.3
|
SECONDARY outcome
Timeframe: 3 months for each drugPopulation: After completion of both of the treatments, it is found in the 3rd month some patients didn't response according to the response rate and during result analysis the responded numbers (48 and 32)were considered only. That's why the number of participant in both the trials didn't match with number of participants analyzed.
Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1:Total Cholesterol(TC) Analysis 2:Triglyceride(TG) Analysis 3:High Density Lipoprotein(HDL) Analysis 4:Low Density Lipoprotein(LDL)
Outcome measures
| Measure |
Pioglitazone (001 Group)
n=48 Participants
Dose: Pioglitazone tablet 30 mg once daily for 3 months
|
Metformin (002 Group)
n=32 Participants
Dose: Metformin tablet 850 mg once daily for 3 months
|
|---|---|---|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
Baseline TC
|
182.0 mg/dl
Standard Deviation 44
|
193.0 mg/dl
Standard Deviation 48.0
|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
3rd month TC
|
178 mg/dl
Standard Deviation 42
|
177.0 mg/dl
Standard Deviation 38.0
|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
Baseline TG
|
183 mg/dl
Standard Deviation 128
|
166.0 mg/dl
Standard Deviation 89.0
|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
3rd month TG
|
195 mg/dl
Standard Deviation 165
|
175.0 mg/dl
Standard Deviation 108.0
|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
Baseline HDL
|
33 mg/dl
Standard Deviation 10
|
34.4 mg/dl
Standard Deviation 9.0
|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
3rd month HDL
|
33.2 mg/dl
Standard Deviation 8
|
34.7 mg/dl
Standard Deviation 7.0
|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
Baseline LDL
|
112.8 mg/dl
Standard Deviation 105.5
|
125.6 mg/dl
Standard Deviation 47.0
|
|
Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin
3rd month LDL
|
105.5 mg/dl
Standard Deviation 47
|
112.0 mg/dl
Standard Deviation 34.0
|
Adverse Events
Pioglitazone (001 Group)
Metformin (002 Group)
Serious adverse events
| Measure |
Pioglitazone (001 Group)
n=77 participants at risk
77 patients received the drug pioglitazone (30mg/day) for 3 months. Adverse events were assessed non-systematically on patients' complain generally and also systematically in case of hypertension, weight gain, common depression \[Patient Health Questionnaire (PHQ-9) method\] and creatinine increase.
No serious adverse event was found during pioglitazone trial.
In case of other adverse event, one patient complained for peripheral edema which disappeared (without medicine) within 2 days at the 2nd month of the treatment, Four patients gained weight within 10% of their initial weight after 3 months of the treatment and two patients complained for abdominal discomfort in the 1st month and normal treatment with antacid was provided to them.
|
Metformin (002 Group)
n=70 participants at risk
After wash out period 70 patients started with metformin (850mg/day) for further 3 months. Adverse events were assessed non-systematically on patients' complain and also systematically in case of hypertension, weight gain, common depression (PHQ-9 method) and creatinine increase.
On basis of systemic data review and patient complain one patient was found with hypertension and another one was with increased creatinine level at the end of the metformin treatment and these events were assumed as serious adverse events as they were at health risk and withdrawn from the trial for intervention by hospital physician though they didn't need for hospitalization.
One patient complained for mild diarrhea in the first month of the metformin treatment, the patient needed necessary treatment according to doctor's advice for one day, Five patients complained for abdominal discomfort in the 1st month and antacid was provided. Six patients were assumed suffering from common depression.
|
|---|---|---|
|
Vascular disorders
Hypertension
|
0.00%
0/77 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
1.4%
1/70 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Renal and urinary disorders
Creatinine increase
|
0.00%
0/77 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
1.4%
1/70 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
Other adverse events
| Measure |
Pioglitazone (001 Group)
n=77 participants at risk
77 patients received the drug pioglitazone (30mg/day) for 3 months. Adverse events were assessed non-systematically on patients' complain generally and also systematically in case of hypertension, weight gain, common depression \[Patient Health Questionnaire (PHQ-9) method\] and creatinine increase.
No serious adverse event was found during pioglitazone trial.
In case of other adverse event, one patient complained for peripheral edema which disappeared (without medicine) within 2 days at the 2nd month of the treatment, Four patients gained weight within 10% of their initial weight after 3 months of the treatment and two patients complained for abdominal discomfort in the 1st month and normal treatment with antacid was provided to them.
|
Metformin (002 Group)
n=70 participants at risk
After wash out period 70 patients started with metformin (850mg/day) for further 3 months. Adverse events were assessed non-systematically on patients' complain and also systematically in case of hypertension, weight gain, common depression (PHQ-9 method) and creatinine increase.
On basis of systemic data review and patient complain one patient was found with hypertension and another one was with increased creatinine level at the end of the metformin treatment and these events were assumed as serious adverse events as they were at health risk and withdrawn from the trial for intervention by hospital physician though they didn't need for hospitalization.
One patient complained for mild diarrhea in the first month of the metformin treatment, the patient needed necessary treatment according to doctor's advice for one day, Five patients complained for abdominal discomfort in the 1st month and antacid was provided. Six patients were assumed suffering from common depression.
|
|---|---|---|
|
Vascular disorders
Peripheral Edema
|
1.3%
1/77 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
0.00%
0/70 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
General disorders
Weight gain
|
5.2%
4/77 • Number of events 4 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
0.00%
0/70 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Gastrointestinal disorders
Mild Diarrhoea
|
0.00%
0/77 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
1.4%
1/70 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.6%
2/77 • Number of events 2 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
7.1%
5/70 • Number of events 5 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Gastrointestinal disorders
Nausea
|
1.3%
1/77 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
2.9%
2/70 • Number of events 2 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Gastrointestinal disorders
Backpain
|
1.3%
1/77 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
1.4%
1/70 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Nervous system disorders
Dizziness
|
1.3%
1/77 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
2.9%
2/70 • Number of events 2 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Nervous system disorders
Headache
|
1.3%
1/77 • Number of events 1 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
2.9%
2/70 • Number of events 2 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
|
Nervous system disorders
Common Depression
|
3.9%
3/77 • Number of events 3 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
8.6%
6/70 • Number of events 6 • 3 months for pioglitazone treatment and next 3 months for metformin treatment
|
Additional Information
Dr. Masuma Parvin
Ministry of Science and Technology, Government of the People's Republic of Bangladesh
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place