Rosiglitazone-Metformin Combination Versus Metformin-Sulfonylurea Combination On Beta-Cell Function In Type 2 Diabetes - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Parallel Assignment
Condition:	Type 2 Diabetes Mellitus
Interventions:	Drug: rosiglitazone-metformin Drug: Metformin Drug: metformin+ gliclazide

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Rosiglitazone + Metformin 4 mg/2 g/Day	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks
Gliclazide + Metformin 80 mg/2 g/Day	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 320 mg/2 g/day after 4 weeks

Participant Flow: Overall Study

	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
STARTED	43	41
COMPLETED	32	30
NOT COMPLETED	11	11
Adverse Event	6	3
Patient's Willing	3	2
Lack of Efficacy	1	2
Lost to Follow-up	1	1
Protocol Violation	0	1
Stopping Criterion Met	0	1
Participant Living oo Far from Hospital	0	1

Baseline Characteristics

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Reporting Groups

	Description
Rosiglitazone + Metformin 4 mg/2 g/Day	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks
Gliclazide + Metformin 80 mg/2 g/Day	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 320 mg/2 g/day after 4 weeks

Baseline Measures

	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day	Total
Number of Participants [units: participants]	43	41	84
Age [units: years] Mean ± Standard Deviation	58.3 ± 8.4	58.1 ± 8.0	58.2 ± 8.2
Gender [units: participants]
Female	11	16	27
Male	32	25	57
Race/Ethnicity, Customized^[1] [units: participants]
Not Collected	43	41	84
Body Mass Index (BMI)^[2] [units: kilograms per square meter (kg/m2)]
<25	3	0	3
25-30	21	20	41
>30	19	21	40
FBG^[3] [units: Millimoles/Liter (mmol/L)] Mean ± Standard Deviation	9.10 ± 1.72	8.28 ± 1.11	8.70 ± 1.50
HbA1c^[4] [units: percentage] Mean ± Standard Deviation	7.5 ± 0.55	7.3 ± 0.55	7.4 ± 0.57

[1]	Region of enrollment, race, and ethnicity data were not collected in this study.
[2]	Number of participants with the indicated class of BMI at randomization
[3]	Mean fasting blood glucose (FBG) levels were measured by blood draw
[4]	Mean hemoglobin A1c (HbA1c) levels were measured by blood draw

Outcome Measures

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1. Primary:

Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment [ Baseline and Month 36 ]

Measure Type	Primary
Measure Title	Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment
Measure Description	Change from baseline in the insulin secretory capacity was measured by the assesement of blood insulin concentrations (conc.) using the hyperglycaemic clamp (HC) technique, per intravenous glucose perfusion by a catheter. Change from baseline for insulin and C-peptide conc peaks (highest conc level) was calculated as the Month 36 value minus the baseline value. Area under the curve (AUC) was measured as pmol/L*min. Insulin secretion was assessed by calculating AUC during the first 10 inches of HC (incremental and total AUC0-10 min) and the AUC after the first 10 inches of the HC (0-180min).
Time Frame	Baseline and Month 36
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: participants receiving at least one dose of study drug with an available efficacy evaluation (HC at M18 or M36). The measurement was conducted on participants who had baseline and M18 and M36 HC test data available. Each HC was validated at both Baseline and Month 36, resulting in different "n"s for each category.

Reporting Groups

	Description
Rosiglitazone + Metformin 4 mg/2 g/Day	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks
Gliclazide + Metformin 80 mg/2 g/Day	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 320 mg/2 g/day after 4 weeks

Measured Values

	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Number of Participants Analyzed [units: participants]	43	41
Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment [units: picomoles/L per minute (pmol/L*min)] Median ( Full Range )
Total AUC(0-10 min), n=24, 26	-3.9 ( -688.3 to 2211.2 )	-75.3 ( -919.9 to 1507.1 )
Incremental AUC(0-10 min), n=22, 23	7.0 ( -308.3 to 2781.2 )	74.6 ( -822.2 to 1193.8 )
Total concentration peak(0-10 min), n=25, 26	-8.6 ( -89.6 to 386.5 )	3.6 ( -121.2 to 52.3 )
Incremental concentration peak(0-10 min), n=24, 26	-1.8 ( -60.9 to 443.8 )	10.8 ( -128.3 to 56.6 )
Total AUC(10-180 min), n=20, 24	40.6 ( -411.9 to 500.2 )	-21.2 ( -344.2 to 787.3 )
Incremental AUC(10-180 min), n=19, 24	67.0 ( -304.2 to 518.4 )	13.6 ( -264.9 to 793.4 )
Total concentration peak(10-180 min), n=27, 29	7.9 ( -223.0 to 286.1 )	-9.3 ( -120.5 to 229.4 )
Incremental concentation peak(10-180 min), n=25,29	10.8 ( -232.3 to 198.6 )	11.5 ( -116.9 to 231.6 )

No statistical analysis provided for Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment

2. Secondary:

Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment [ Baseline and Month 18 ]

Measure Type	Secondary
Measure Title	Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment
Measure Description	Change from baseline was calculated as the Month 18 value minus the baseline value. Insulin secretion capacity is measured in blood (blood level of insulin) and is a response of the pancreatic beta-cells to hyperglycemia induced by a glucose IV bolus, then infusion. Hyperglycemic clamp is a reference technique to evaluate the initial and the secondary phases of insulin secretion.
Time Frame	Baseline and Month 18
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: participants receiving at least one dose of study drug with an available efficacy evaluation (HC at M18 or M36). The measurement was conducted on participants who had baseline and M18 and M36 HC test data available. Each HC was validated at both Baseline and Month 36, resulting in different "n"s for each category.

Reporting Groups

	Description
Rosiglitazone + Metformin 4 mg/2 g/Day	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks
Gliclazide + Metformin 80 mg/2 g/Day	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 320 mg/2 g/day after 4 weeks

Measured Values

	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Number of Participants Analyzed [units: participants]	43	41
Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment [units: pmol/L*min] Median ( Full Range )
HC, Total AUC(0-10min), n=30, 31	18.3 ( -1044.7 to 2211.2 )	-32.3 ( -919.9 to 1612.5 )
HC, Incremental AUC(0-10min), n=27, 26	22.3 ( -308.3 to 2781.2 )	60.7 ( -822.2 to 1193.8 )
HC, Total AUC(10-180min), n=26, 30	55.9 ( -411.9 to 500.2 )	-7.6 ( -344.2 to 787.3 )
HC, Incremental AUC(10-180min), n=26, 29	72.9 ( -304.2 to 518.4 )	14.6 ( -264.9 to 1172.7 )
Arginine (Arg) test, Total AUC(0-30min), n=25, 25	38.4 ( -367.0 to 225.0 )	10.9 ( -163.9 to 93.1 )
Arg test, Incremental AUC(0-30min), n=25, 25	15.1 ( -440.3 to 120.9 )	-8.0 ( -153.3 to 49.3 )
Arg test, Incremental Conc. peak(0-30 min),n=26,29	23.3 ( -2531.7 to 766.5 )	-111.1 ( -1125.0 to 499.7 )

No statistical analysis provided for Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment

3. Secondary:

Mean Change From Baseline in HbA1c at Month 36 [ Baseline and Month 36 ]

Measure Type	Secondary
Measure Title	Mean Change From Baseline in HbA1c at Month 36
Measure Description	Change from baseline was calculated as the Month 36 value minus the baseline value. HbA1c levels were measured by blood draw.
Time Frame	Baseline and Month 36
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug and had an available efficacy evaluation (hyperglycaemic clamp at M18 or M36). This measurement was conducted on participants in the ITT Population who had baseline and M18 and M36 clamp test data available.

Reporting Groups

	Description
Rosiglitazone + Metformin 4 mg/2 g/Day	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks
Gliclazide + Metformin 80 mg/2 g/Day	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 320 mg/2 g/day after 4 weeks

Measured Values

	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Number of Participants Analyzed [units: participants]	32	31
Mean Change From Baseline in HbA1c at Month 36 [units: percentage] Mean ± Standard Deviation	-0.22 ± 1.3	0.3 ± 1.2

No statistical analysis provided for Mean Change From Baseline in HbA1c at Month 36

4. Secondary:

Mean Change From Baseline in FBG at Month 36 [ Baseline and Month 36 ]

Measure Type	Secondary
Measure Title	Mean Change From Baseline in FBG at Month 36
Measure Description	Change from baseline was calculated as the Month 36 value minus the baseline value. FBG levels were measured by blood draw.
Time Frame	Baseline and Month 36
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug and had an available efficacy evaluation (hyperglycaemic clamp at M18 or M36). This measurement was conducted on participants in the ITT Population who had baseline and M18 and M36 clamp test data available.

Reporting Groups

	Description
Rosiglitazone + Metformin 4 mg/2 g/Day	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks
Gliclazide + Metformin 80 mg/2 g/Day	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 320 mg/2 g/day after 4 weeks

Measured Values

	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Number of Participants Analyzed [units: participants]	32	30
Mean Change From Baseline in FBG at Month 36 [units: mmol/L] Mean ± Standard Deviation	-1.6 ± 1.9	-0.2 ± 2.4

No statistical analysis provided for Mean Change From Baseline in FBG at Month 36

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	101765, AVAF4001
Study First Received:	August 21, 2006
Results First Received:	October 2, 2009
Last Updated:	October 2, 2009
ClinicalTrials.gov Identifier:	NCT00367055 History of Changes
Health Authority:	France: National Consultative Ethics Committee for Health and Life Sciences