Efficacy of Pioglitazone/Metformin Combination Therapy in... | NCT00770653

ID	Type	Description
2006-004455-37	EudraCT Number
D-PIO-114	Other Identifier	Takeda Pharma GmbH
U1111-1114-1678	Registry Identifier	WHO

Label	Type	Description	Intervention Names
Pioglitazone 15 mg and Metformin 850 mg BID	Experimental		Drug: Pioglitazone and Metformin
Glimepiride 2 mg and Metformin 850 mg BID	Active Comparator		Drug: Glimepiride and Metformin

Name	Type	Description	Arm Group Labels	Other Names
Pioglitazone and Metformin	Drug	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.

Measure	Description	Time Frame
The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol.	The increase in High-Density Lipoprotein (HDL) Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.	Baseline and Week 24.

Measure	Description	Time Frame
Change From Baseline in High-Density Lipoprotein Cholesterol.	The change between HDL-Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.	Baseline and Week 24.
Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio.

Name	Affiliation	Role
Medical Adviser Clinical Research	Takeda Pharma Gmbh, Aachen (Germany)	Study Director

PubMed Identifier	Type	Citation	Retractions
21457065	Derived	Pfutzner A, Schondorf T, Tschope D, Lobmann R, Merke J, Muller J, Lehmann U, Fuchs W, Forst T. PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with glimepiride on diabetic dyslipidemia. Diabetes Technol Ther. 2011 Jun;13(6):637-43. doi: 10.1089/dia.2010.0233. Epub 2011 Apr 2.

Label	URL
ACTOPLUS MET® Package Insert	View source

ID	Title	Description
FG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
FG001	Glimepiride 2 mg and Metformin 850 mg BID

Primary

The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol.

The increase in High-Density Lipoprotein (HDL) Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.

Analysis was performed on participants with at least one valid baseline and post-baseline measurement. This condition was not fulfilled in 17 participants who were excluded from the all-participants-randomized set, leading to a full-analysis-set of 288 (146 vs. 142). Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants	OG000146 OG001142

Title

Denominators

Categories

Title	Measurements
	OG0003.2± 9.7 OG001-0.3± 11.0

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis (H0) = mean increase of HDL after 24 weeks of treatment of Pio/Met group ≤ the mean increase in the Gli/Met group. Alternate hypothesis (H1) = mean increase of HDL after 24 weeks of treatment of Pio/Met group > the mean increase in the Gli/Met group. The relevant clinical effect size to detect with adequate power was 0.35. With this assumption, a one sided t-test with a type I error rate had 80% power to reject the H0 for the H1 when the sample size was 130 patients per group.	ANCOVA		0.0018		Mean Difference (Final Values)	3.2670			2-Sided	95	1.2264	5.3076				No	Superiority or Other

Secondary

Change From Baseline in High-Density Lipoprotein Cholesterol.

The change between HDL-Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio.

The change between High-Density Lipoprotein/Low-Density Lipoprotein Ratio collected at week 24 or final visit and High-Density Lipoprotein/Low-Density Lipoprotein Ratio collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Triglycerides.

The change between the value of Triglycerides collected at week 24 or final visit and Triglycerides collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Low-Density Lipoprotein Subfractions.

The change between the value of Low-Density Lipoprotein Subfractions collected at week 24 or final visit and Low-Density Lipoprotein Subfractions collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Low-Density Lipoprotein Cholesterol.

The change between Low-Density Lipoprotein Cholesterol collected at week 24 or final visit and Low-Density Lipoprotein Cholesterol collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Glycosylated Hemoglobin.

The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 or final visit and Glycosylated Hemoglobin collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Fasting Intact Proinsulin.

The change between Fasting Intact Proinsulin collected at week 24 or final visit and Fasting Intact Proinsulin collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

pmol/L

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Fasting Glucose.

The change between Fasting Glucose collected at week 24 or final visit and Fasting Glucose collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Adiponectin.

The change between Adiponectin collected at week 24 or final visit and Adiponectin collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

μg/mL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in High Sensitivity C-reactive Protein (Original).

The change between the value of High Sensitivity C-reactive Protein collected at week 24 or final visit and High Sensitivity C-reactive Protein collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mg/L

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L).

The change between the value of High Sensitivity C-reactive Protein less than or equal to 10 mg/L collected at week 24 or final visit and High Sensitivity C-reactive Protein less than or equal to 10 mg/L collected at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

mg/L

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Systolic Blood Pressure.

The change between Systolic Blood Pressure measured at week 24 or final visit and Systolic Blood Pressure measured at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Diastolic Blood Pressure.

The change between Diastolic Blood Pressure measured at week 24 or final visit and Diastolic Blood Pressure measured at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Deviation

mmHg

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Intake of Study Medication Greater Than 80% and Less Than 120%.

The change between the Intake of study medication greater than 80% at week 24 or final visit and Baseline and the Intake of study medication greater than 80% at baseline.

Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Number

participants

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Nitrotyrosine.

The change between the value of Nitrotyrosine collected at week 24 or final visit and Nitrotyrosine collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

nmol/L

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Soluble CD40 Ligand.

The change between the value of Soluble CD40 Ligand collected at week 24 or final visit and Soluble CD40 Ligand collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

pg/mL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Matrix Metallo Proteinase-9.

The change between the value of Baseline in Matrix Metallo Proteinase-9 collected at week 24 or final visit and Baseline in Matrix Metallo Proteinase-9 collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

ng/mL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Soluble Intracellular Adhesion Molecule.

The change between the value of Baseline in Soluble Intracellular Adhesion molecule at week 24 or final visit and Baseline in Soluble Intracellular Adhesion molecule collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

ng/mL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Soluble Vascular Cell Adhesion Molecule.

The change between the value of Soluble Vascular Cell Adhesion Molecule collected at week 24 or final visit and Soluble Vascular Cell Adhesion Molecule collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

ng/mL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Thromboxane B2.

The change between the value of Thromboxane B2 collected at week 24 or final visit and Thromboxane B2 collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

pg/mL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Platelet Function.

The change between the value of Platelet Function by PFA 100 collected at week 24 or final visit and Platelet Function by PFA 100 collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

sec

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in E-Selectin.

The change between the value of E-Selectin collected at week 24 or final visit and E-Selectin collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

ng/mL

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Von-Willebrand Factor.

The change between the value of Von-Willebrand Factor collected at week 24 or final visit and Von-Willebrand Factor collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Least Squares Mean

Standard Error

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Erythrocyte Deformability (0.30%).

The change between the 0.30 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Erythrocyte Deformability (0.60%)

The change between the 0.60 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Erythrocyte Deformability (1.20).

The change between the 1.20 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Erythrocyte Deformability (3.00).

The change between the 3.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Erythrocyte Deformability (6.00).

The change between the 6.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Erythrocyte Deformability (12.00).

The change between the 12.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Erythrocyte Deformability (30.00).

The change between the 30.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Secondary

Change From Baseline in Erythrocyte Deformability (60.00).

The change between the 60.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.

Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.

Posted

Mean

Standard Deviation

percent

Baseline and Week 24.

ID	Title	Description
OG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
OG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Units	Counts

Facility	Status	City	State	ZIP	Country	Contacts
		Bretten	Baden-Wurttemberg		Germany

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.			17	153	61	153
EG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.			8	149	61	149

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal adhesions	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk
Benign breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Cardiac failure	Cardiac disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected153 at risk EG0010 affected149 at risk
Cardiomegaly	Cardiac disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk
Chest pain	General disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Coronary artery disease	Cardiac disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk
Depression	Psychiatric disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Hypertensive crisis	Vascular disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Mental disorder due to a general medical condition	Psychiatric disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Subileus	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk
Tachycardia	Cardiac disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Tumour marker increased	Investigations	MedDRA 11.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected149 at risk
Urinary retention	Renal and urinary disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected149 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 11.0	Systematic Assessment	EG0008 affected153 at risk EG0013 affected149 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG00014 affected153 at risk EG00114 affected149 at risk
Headache	Nervous system disorders	MedDRA 11.0	Systematic Assessment	EG0007 affected153 at risk EG0017 affected149 at risk
Nasopharyngitis	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG00024 affected153 at risk EG00133 affected149 at risk
Oedema peripheral	General disorders	MedDRA 11.0	Systematic Assessment	EG0008 affected153 at risk EG0014 affected149 at risk

ID	Term
D003920	Diabetes Mellitus
D050171	Dyslipidemias
D044882	Glucose Metabolism Disorders
D003924	Diabetes Mellitus, Type 2
D003923	Diabetes Mellitus, Lipoatrophic
D006949	Hyperlipidemias

ID	Title	Description
BG000	Pioglitazone 15 mg and Metformin 850 mg BID	Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
BG001	Glimepiride 2 mg and Metformin 850 mg BID	Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
BG002	Total	Total of all reporting groups

ID	Term
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D052439	Lipid Metabolism Disorders

ID	Term
D045162	Thiazolidinediones
D013844	Thiazoles
D013457	Sulfur Compounds
D009930	Organic Chemicals
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001645	Biguanides
D006146	Guanidines
D000578	Amidines