Trial Outcomes & Findings for Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone (NCT NCT00121667)

NCT ID: NCT00121667

Last Updated: 2015-04-29

Results Overview

Mean change from baseline is adjusted for baseline value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1462 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2015-04-29

Participant Flow

1462 participants were enrolled, and 787 entered the lead-in period. 45 discontinued the during the lead-in period. 19 subjects no longer met study criteria, 10 subjects withdrew consent, and 2 subjects were randomized but not treated.

Participant milestones

Participant milestones
Measure	Saxagliptin 2.5 mg + Metformin Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 5 mg + Metformin Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Short Term (ST) Period STARTED	192	191	181	179
Short Term (ST) Period COMPLETED	148	143	140	112
Short Term (ST) Period NOT COMPLETED	44	48	41	67
Short Term (ST) + Long Term (LT) Period STARTED	192	191	181	179
Short Term (ST) + Long Term (LT) Period Completed Study Without Being Rescued	14	18	23	7
Short Term (ST) + Long Term (LT) Period COMPLETED	64	58	68	39
Short Term (ST) + Long Term (LT) Period NOT COMPLETED	128	133	113	140

Reasons for withdrawal

Reasons for withdrawal
Measure	Saxagliptin 2.5 mg + Metformin Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 5 mg + Metformin Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Short Term (ST) Period Lack of Efficacy	25	22	27	44
Short Term (ST) Period Subject Withdrew Consent	8	13	4	11
Short Term (ST) Period Adverse Event	5	6	5	3
Short Term (ST) Period Lost to Follow-up	3	4	4	3
Short Term (ST) Period Poor / Non-compliance	0	1	1	2
Short Term (ST) Period Subject No Longer Meets Study Criteria	0	2	0	2
Short Term (ST) Period Other Reason	3	0	0	0
Short Term (ST) Period Death	0	0	0	1
Short Term (ST) Period Pregnancy	0	0	0	1
Short Term (ST) + Long Term (LT) Period Lack of Efficacy	54	51	42	65
Short Term (ST) + Long Term (LT) Period Subject Withdrew Consent	38	34	26	30
Short Term (ST) + Long Term (LT) Period Adverse Event	12	18	13	10
Short Term (ST) + Long Term (LT) Period Lost to Follow-up	11	11	13	16
Short Term (ST) + Long Term (LT) Period Other Reason	5	7	6	3
Short Term (ST) + Long Term (LT) Period Subject No Longer Meets Study Criteria	3	6	5	9
Short Term (ST) + Long Term (LT) Period Poor / Non-compliance	3	5	8	4
Short Term (ST) + Long Term (LT) Period Pregnancy	1	1	0	1
Short Term (ST) + Long Term (LT) Period Death	1	0	0	2

Baseline Characteristics

Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Total n=743 Participants Total of all reporting groups
Age, Continuous	54.66 years STANDARD_DEVIATION 10.08 • n=5 Participants	54.69 years STANDARD_DEVIATION 9.62 • n=7 Participants	54.18 years STANDARD_DEVIATION 10.14 • n=5 Participants	54.76 years STANDARD_DEVIATION 10.18 • n=4 Participants	54.57 years STANDARD_DEVIATION 9.98 • n=21 Participants
Age, Customized < 65 years	159 participants n=5 Participants	159 participants n=7 Participants	155 participants n=5 Participants	153 participants n=4 Participants	626 participants n=21 Participants
Age, Customized >= 65 years	33 participants n=5 Participants	32 participants n=7 Participants	26 participants n=5 Participants	26 participants n=4 Participants	117 participants n=21 Participants
Age, Customized >= 75 years	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants	3 participants n=4 Participants	13 participants n=21 Participants
Sex: Female, Male Female	109 Participants n=5 Participants	88 Participants n=7 Participants	86 Participants n=5 Participants	83 Participants n=4 Participants	366 Participants n=21 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	103 Participants n=7 Participants	95 Participants n=5 Participants	96 Participants n=4 Participants	377 Participants n=21 Participants
Race/Ethnicity, Customized White	153 participants n=5 Participants	159 participants n=7 Participants	144 participants n=5 Participants	150 participants n=4 Participants	606 participants n=21 Participants
Race/Ethnicity, Customized Black / African American	8 participants n=5 Participants	11 participants n=7 Participants	14 participants n=5 Participants	7 participants n=4 Participants	40 participants n=21 Participants
Race/Ethnicity, Customized Asian	8 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	4 participants n=4 Participants	20 participants n=21 Participants
Race/Ethnicity, Customized Other	23 participants n=5 Participants	18 participants n=7 Participants	18 participants n=5 Participants	18 participants n=4 Participants	77 participants n=21 Participants
Race/Ethnicity, Customized Hispanic / Latino	27 participants n=5 Participants	25 participants n=7 Participants	29 participants n=5 Participants	27 participants n=4 Participants	108 participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic / Latino	64 participants n=5 Participants	62 participants n=7 Participants	54 participants n=5 Participants	49 participants n=4 Participants	229 participants n=21 Participants
Race/Ethnicity, Customized Not Reported	101 participants n=5 Participants	104 participants n=7 Participants	98 participants n=5 Participants	103 participants n=4 Participants	406 participants n=21 Participants
Age Characterization Female Only =< 50 years	33 participants n=5 Participants	34 participants n=7 Participants	24 participants n=5 Participants	21 participants n=4 Participants	112 participants n=21 Participants
Age Characterization Female Only > 50 years	76 participants n=5 Participants	54 participants n=7 Participants	62 participants n=5 Participants	62 participants n=4 Participants	254 participants n=21 Participants
Weight	85.97 kg STANDARD_DEVIATION 17.57 • n=5 Participants	87.26 kg STANDARD_DEVIATION 17.04 • n=7 Participants	87.83 kg STANDARD_DEVIATION 18.90 • n=5 Participants	87.14 kg STANDARD_DEVIATION 17.75 • n=4 Participants	87.04 kg STANDARD_DEVIATION 17.79 • n=21 Participants
Body Mass Index	31.68 kg/m^2 STANDARD_DEVIATION 5.15 • n=5 Participants	31.23 kg/m^2 STANDARD_DEVIATION 4.67 • n=7 Participants	31.12 kg/m^2 STANDARD_DEVIATION 4.79 • n=5 Participants	31.57 kg/m^2 STANDARD_DEVIATION 4.80 • n=4 Participants	31.40 kg/m^2 STANDARD_DEVIATION 4.85 • n=21 Participants
Body Mass Index Categorization < 30	75 Participants n=5 Participants	84 Participants n=7 Participants	82 Participants n=5 Participants	76 Participants n=4 Participants	317 Participants n=21 Participants
Body Mass Index Categorization >= 30	117 Participants n=5 Participants	107 Participants n=7 Participants	99 Participants n=5 Participants	103 Participants n=4 Participants	426 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Randomized participants with both a baseline and post-baseline value (up to Week 24)

Mean change from baseline is adjusted for baseline value.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=186 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=186 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=180 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=175 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24 Baseline Mean	8.07 percentage of glycosylated hemoglobins Standard Error 0.06	8.08 percentage of glycosylated hemoglobins Standard Error 0.07	7.98 percentage of glycosylated hemoglobins Standard Error 0.08	8.06 percentage of glycosylated hemoglobins Standard Error 0.07
Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24 Adjusted Mean Change from Baseline	-0.69 percentage of glycosylated hemoglobins Standard Error 0.07	-0.59 percentage of glycosylated hemoglobins Standard Error 0.07	-0.58 percentage of glycosylated hemoglobins Standard Error 0.07	0.13 percentage of glycosylated hemoglobins Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Randomized Participants with measurement at timepoint. Last Observation Carried Forward (LOCF).

Mean change from baseline is adjusted for baseline value.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=187 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=188 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=176 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 Baseline Mean	179.03 mg/dL Standard Error 3.44	173.57 mg/dL Standard Error 3.23	175.86 mg/dL Standard Error 3.73	174.94 mg/dL Standard Error 3.27
Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 Adjusted Mean Change from Baseline	-22.03 mg/dL Standard Error 2.49	-14.31 mg/dL Standard Error 2.48	-20.50 mg/dL Standard Error 2.53	1.24 mg/dL Standard Error 2.56

SECONDARY outcome

Timeframe: Week 24

Population: Randomized Participants with measurement at time point, Last Observation Carried Forward (LOCF)

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=186 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=186 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=180 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=175 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24	43.5 percentage of participants	37.1 percentage of participants	44.4 percentage of participants	16.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Randomized Participants with measurement at timepoint. Last Observation Carried Forward (LOCF).

Mean change from baseline is adjusted for baseline value.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=146 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=150 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=148 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=131 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) Baseline Mean	49021 mg*min/dL Standard Error 876.17	48224 mg*min/dL Standard Error 869.70	44931 mg*min/dL Standard Error 889.85	47407 mg*min/dL Standard Error 1071.9
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) Adjusted Mean Change from Baseline	-9586 mg*min/dL Standard Error 810.46	-8891 mg*min/dL Standard Error 797.97	-8137 mg*min/dL Standard Error 807.88	-3291 mg*min/dL Standard Error 853.24

OTHER_PRE_SPECIFIED outcome

Timeframe: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla

Population: All treated participants

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related events=relationship of certain, probable, possible, or missing.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 AE	155 participants	177 participants	161 participants	142 participants
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 Related AE	57 participants	53 participants	65 participants	56 participants
Overall Summary of Adverse Events During ST+LT Treatment Period Deaths	0 participants	1 participants	1 participants	2 participants
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 SAE	27 participants	23 participants	22 participants	15 participants
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 Related SAE	3 participants	0 participants	1 participants	1 participants
Overall Summary of Adverse Events During ST+LT Treatment Period Discontinuations Due to SAEs	6 participants	4 participants	6 participants	0 participants
Overall Summary of Adverse Events During ST+LT Treatment Period Discontinuations Due to AEs	18 participants	11 participants	13 participants	9 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Lab assessments taken during and up to 14 days after the last dose of study drug during the ST + LT Treatment Period. Mean duration of exposure: 124, 118, 130, 95 weeks, respectively, for 2.5mg, 5mg, 10 mg, placebo.

Population: Number of Participants Analyzed=Treated participants; n=number of treated subjects with baseline value and at least one value during the ST + LT treatment period

A laboratory value was considered a marked abnormality if it is outside the pre-defined criteria for marked abnormality and the on-treatment value was more extreme (farther from the limit) than the baseline value. Pre-Rx=pretreatment; ULN=upper limit of normal; ALP=alkaline phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase; unspec=unspecified; sodium serum low: \<0.9 x Pre-Rx \& \<=130mEq/L / high: \>1.1 x Pre-Rx \& \>=150mEq/L; potassium, serum low: \<=0.8 x Pre-Rx \& \>=6.0mEq/L / high: 1.2 x Pre-Rx \& \>=6.0mEq/L; LLN=lower limit of normal.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Marked Laboratory Abnormalities - During ST + LT Treatment Period Neutrophils+Bands <1x1000 c/µL (n=189,190,181,179)	1 participants	1 participants	0 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Leukocytes < 2 x 1000 c/µL (n=189, 190, 181, 179)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALP >3 x pre-Rx and >ULN (n=190, 190, 181, 179)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Hemoglobin < 8 g/dL (n=189, 190, 181, 179)	1 participants	1 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Hematocrit < 0.75 x pre-Rx (n=189, 190, 181, 179)	5 participants	2 participants	5 participants	2 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Platelets < 50 x 10^9 c/L (n=189, 188, 181, 178)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Platelets > 1.5 x ULN (n=189, 188, 181, 178)	0 participants	0 participants	4 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Eosinophils >0.9x1000 c/µL (n=189, 190, 181, 179)	12 participants	12 participants	18 participants	9 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Lymphocytes <=0.75x1000 c/µL (n=189,190,181,179)	4 participants	3 participants	4 participants	2 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALP >1.5 x ULN (n=190, 190, 181, 179)	1 participants	3 participants	1 participants	3 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >3 x ULN (n=190, 190, 181, 179)	1 participants	6 participants	3 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >5 x ULN (n=190, 190, 181, 179)	0 participants	1 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Uric Acid > 1.5 x ULN (n=0, 0, 0, 0)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >10 x ULN (n=190, 190, 181, 179)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >20 x ULN (n=190, 190, 181, 179)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >3 x ULN (n=190, 190, 181, 179)	4 participants	4 participants	4 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >5 x ULN (n=190, 190, 181, 179)	0 participants	1 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >10 x ULN (n=190, 190, 181, 179)	0 participants	1 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >20 x ULN (n=190, 190, 181, 179)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Bilirubin Total >2mg/dL (n=190,190,181,179)	1 participants	2 participants	0 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Bilirubin Total >1.5xULN (n=190,190,181,179)	1 participants	2 participants	0 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Bilirubin Total >2xULN (n=190,190,181,179)	1 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period BUN >2 x pre-Rx and >ULN (n=190,190,181,179)	9 participants	12 participants	6 participants	9 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Creatinine >2.5 mg/dL (n=190,190,181,179)	1 participants	1 participants	1 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose, Serum Fasting < 50 mg/dL (n=0, 0, 0, 0)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose, Serum Fasting > 500 mg/dL (n=0, 0, 0, 0)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose, Serum Unspec. < 50 mg/dL (n=0,0,0,0)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose, Serum Unspec. > 500 mg/dL (n=0,0,0,0)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose, Plasma Fasting<50mg/dL(n=189,189,181,179)	3 participants	2 participants	1 participants	3 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose,Plasma Fasting>500mg/dL(n=189,189,181,179)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Protein Urine, >=2-4 (n=187, 189, 180, 178)	9 participants	7 participants	13 participants	12 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose, Plasma Unspec.<50mg/dL(n=192,191,181,179)	7 participants	19 participants	9 participants	9 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose,Plasma Unspec.>500mg/dL(n=192,191,181,179)	1 participants	1 participants	1 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Sodium,Serum Low (*) (n=190,190,181,179)	2 participants	1 participants	4 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Sodium,Serum High (*) (n=190,190,181,179)	0 participants	0 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Potassium, Serum Low (*) (n=190,190,181,179)	1 participants	0 participants	1 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Potassium, Serum High (n=190,190,181,179)	5 participants	4 participants	5 participants	7 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Chloride < 90 mEq/L (n=190, 190, 181, 179)	3 participants	2 participants	3 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Chloride > 120 mEq/L (n=190, 190, 181, 179)	0 participants	1 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Albumin < 0.9 LLN (n=190, 190, 181, 179)	0 participants	1 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Creatine Kinase > 5 x ULN (n=190, 190, 181, 179)	2 participants	1 participants	3 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Blood Urine, >=2-4 (n=187, 189, 180, 178)	21 participants	17 participants	18 participants	13 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Red Blood Cells Urine >=2-4 (n=175,176,162,166)	27 participants	28 participants	22 participants	20 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period White Blood Cells Urine >=2-4 (n=175,176,162,166)	38 participants	43 participants	26 participants	28 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206

Population: Treated participants; n=number of treated participants with measurement at time point

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 206 (n=61, 50, 64, 31)	-0.87 g/dL Standard Error 0.135	-0.62 g/dL Standard Error 0.108	-0.49 g/dL Standard Error 0.101	-0.75 g/dL Standard Error 0.125
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 193 (n=70, 60, 72, 40)	-0.82 g/dL Standard Error 0.159	-0.60 g/dL Standard Error 0.103	-0.47 g/dL Standard Error 0.101	-0.53 g/dL Standard Error 0.134
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 141 (n=85, 79, 85, 48)	-0.45 g/dL Standard Error 0.093	-0.49 g/dL Standard Error 0.091	-0.42 g/dL Standard Error 0.104	-0.45 g/dL Standard Error 0.132
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 154 (n=81, 74, 78, 45)	-0.56 g/dL Standard Error 0.105	-0.59 g/dL Standard Error 0.092	-0.47 g/dL Standard Error 0.102	-0.57 g/dL Standard Error 0.107
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 167 (n=77, 67, 75, 42)	-0.58 g/dL Standard Error 0.127	-0.49 g/dL Standard Error 0.085	-0.53 g/dL Standard Error 0.119	-0.51 g/dL Standard Error 0.137
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 180 (n=70, 61, 73, 41)	-0.81 g/dL Standard Error 0.154	-0.62 g/dL Standard Error 0.099	-0.46 g/dL Standard Error 0.107	-0.53 g/dL Standard Error 0.129
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Baseline (BL) (Week 0) (n=192, 191, 181, 179)	14.18 g/dL Standard Error 0.094	14.06 g/dL Standard Error 0.098	14.18 g/dL Standard Error 0.103	13.99 g/dL Standard Error 0.096
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 2 (n=181, 177, 172, 169)	-0.18 g/dL Standard Error 0.052	-0.08 g/dL Standard Error 0.044	-0.18 g/dL Standard Error 0.044	-0.09 g/dL Standard Error 0.046
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 4 (n=178, 178, 174, 166)	-0.15 g/dL Standard Error 0.047	-0.07 g/dL Standard Error 0.052	-0.09 g/dL Standard Error 0.053	0.03 g/dL Standard Error 0.056
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 6 (n=176, 174, 166, 160)	-0.15 g/dL Standard Error 0.050	-0.06 g/dL Standard Error 0.052	-0.07 g/dL Standard Error 0.050	0.00 g/dL Standard Error 0.055
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 8 (n=173, 176, 165, 157)	-0.07 g/dL Standard Error 0.051	-0.07 g/dL Standard Error 0.058	-0.02 g/dL Standard Error 0.055	0.01 g/dL Standard Error 0.056
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 10 (n=149, 134, 137, 131)	-0.17 g/dL Standard Error 0.057	-0.16 g/dL Standard Error 0.061	-0.16 g/dL Standard Error 0.067	-0.16 g/dL Standard Error 0.064
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 12 (n=170, 167, 160, 144)	-0.11 g/dL Standard Error 0.054	-0.05 g/dL Standard Error 0.059	0.03 g/dL Standard Error 0.055	-0.05 g/dL Standard Error 0.065
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 14 (n=156, 154, 146, 139)	-0.20 g/dL Standard Error 0.055	-0.15 g/dL Standard Error 0.059	-0.10 g/dL Standard Error 0.068	-0.02 g/dL Standard Error 0.066
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 16 (n=167, 166, 159, 140)	-0.13 g/dL Standard Error 0.052	-0.12 g/dL Standard Error 0.059	-0.10 g/dL Standard Error 0.060	-0.01 g/dL Standard Error 0.060
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 18 (n=155, 158, 149, 141)	-0.28 g/dL Standard Error 0.050	-0.24 g/dL Standard Error 0.069	-0.19 g/dL Standard Error 0.059	-0.09 g/dL Standard Error 0.062
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 20 (n=162, 153, 154, 147)	-0.23 g/dL Standard Error 0.061	-0.16 g/dL Standard Error 0.059	-0.10 g/dL Standard Error 0.060	-0.12 g/dL Standard Error 0.060
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 22 (n=157, 152, 143, 138)	-0.33 g/dL Standard Error 0.063	-0.21 g/dL Standard Error 0.064	-0.25 g/dL Standard Error 0.062	-0.23 g/dL Standard Error 0.065
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 24 (n=164, 160, 159, 137)	-0.30 g/dL Standard Error 0.063	-0.23 g/dL Standard Error 0.064	-0.25 g/dL Standard Error 0.057	-0.24 g/dL Standard Error 0.065
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 30 (n=161, 155, 154, 137)	-0.29 g/dL Standard Error 0.063	-0.19 g/dL Standard Error 0.059	-0.22 g/dL Standard Error 0.071	-0.18 g/dL Standard Error 0.065
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 37 (n=152, 149, 146, 122)	-0.29 g/dL Standard Error 0.064	-0.17 g/dL Standard Error 0.068	-0.19 g/dL Standard Error 0.067	-0.17 g/dL Standard Error 0.066
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 50 (n=151, 142, 146, 127)	-0.22 g/dL Standard Error 0.070	-0.22 g/dL Standard Error 0.061	-0.13 g/dL Standard Error 0.066	-0.12 g/dL Standard Error 0.077
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 63 (n=148, 137, 142, 116)	-0.28 g/dL Standard Error 0.096	-0.10 g/dL Standard Error 0.068	-0.17 g/dL Standard Error 0.067	-0.07 g/dL Standard Error 0.073
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 76 (n=134, 126, 130, 94)	-0.31 g/dL Standard Error 0.080	-0.27 g/dL Standard Error 0.077	-0.26 g/dL Standard Error 0.066	-0.26 g/dL Standard Error 0.083
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 89 (n=123, 114, 123, 85)	-0.38 g/dL Standard Error 0.075	-0.22 g/dL Standard Error 0.074	-0.32 g/dL Standard Error 0.083	-0.25 g/dL Standard Error 0.088
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 102 (n=108, 104, 112, 70)	-0.40 g/dL Standard Error 0.085	-0.36 g/dL Standard Error 0.073	-0.27 g/dL Standard Error 0.078	-0.34 g/dL Standard Error 0.100
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 115 (n=99, 94, 98, 58)	-0.26 g/dL Standard Error 0.082	-0.26 g/dL Standard Error 0.073	-0.36 g/dL Standard Error 0.092	-0.26 g/dL Standard Error 0.106
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 128 (n=92, 88, 90, 52)	-0.41 g/dL Standard Error 0.097	-0.40 g/dL Standard Error 0.095	-0.39 g/dL Standard Error 0.095	-0.28 g/dL Standard Error 0.105

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206

Population: Treated participants; n=number of treated participants with measurement at time point

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206

Population: Treated participants; n=number of treated participants with measurement at time point

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Baseline (Week 0) (n=192, 191, 181, 179)	0.23 10^3 c/µL Standard Error 0.016	0.24 10^3 c/µL Standard Error 0.018	0.24 10^3 c/µL Standard Error 0.024	0.21 10^3 c/µL Standard Error 0.013
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 2 (n=178, 175, 170, 169)	0.01 10^3 c/µL Standard Error 0.010	-0.02 10^3 c/µL Standard Error 0.014	-0.00 10^3 c/µL Standard Error 0.013	0.00 10^3 c/µL Standard Error 0.007
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 4 (n=176, 175, 170, 166)	-0.01 10^3 c/µL Standard Error 0.011	-0.01 10^3 c/µL Standard Error 0.023	-0.02 10^3 c/µL Standard Error 0.016	0.00 10^3 c/µL Standard Error 0.007
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 6 (n=175, 172, 165, 158)	-0.01 10^3 c/µL Standard Error 0.012	-0.02 10^3 c/µL Standard Error 0.017	-0.03 10^3 c/µL Standard Error 0.012	0.01 10^3 c/µL Standard Error 0.009
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 8 (n=172, 172, 163, 153)	-0.01 10^3 c/µL Standard Error 0.011	-0.00 10^3 c/µL Standard Error 0.019	-0.02 10^3 c/µL Standard Error 0.011	0.00 10^3 c/µL Standard Error 0.010
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 10 (n=148, 130, 137, 128)	-0.01 10^3 c/µL Standard Error 0.019	-0.02 10^3 c/µL Standard Error 0.012	-0.02 10^3 c/µL Standard Error 0.015	0.01 10^3 c/µL Standard Error 0.011
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 12 (n=168, 166, 159, 141)	-0.01 10^3 c/µL Standard Error 0.013	-0.02 10^3 c/µL Standard Error 0.019	-0.03 10^3 c/µL Standard Error 0.013	0.00 10^3 c/µL Standard Error 0.009
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 14 (n=156, 152, 145, 136)	-0.01 10^3 c/µL Standard Error 0.014	0.01 10^3 c/µL Standard Error 0.022	-0.02 10^3 c/µL Standard Error 0.016	0.02 10^3 c/µL Standard Error 0.013
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 16 (n=166, 166, 157, 137)	0.00 10^3 c/µL Standard Error 0.012	-0.02 10^3 c/µL Standard Error 0.023	-0.02 10^3 c/µL Standard Error 0.014	0.04 10^3 c/µL Standard Error 0.016
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 18 (n=155, 157, 149, 139)	-0.00 10^3 c/µL Standard Error 0.017	-0.01 10^3 c/µL Standard Error 0.015	-0.00 10^3 c/µL Standard Error 0.013	0.04 10^3 c/µL Standard Error 0.015
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 20 (n=162, 153, 154, 146)	-0.01 10^3 c/µL Standard Error 0.014	-0.04 10^3 c/µL Standard Error 0.016	-0.02 10^3 c/µL Standard Error 0.021	0.02 10^3 c/µL Standard Error 0.013
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 22 (n=157, 151, 143, 138)	-0.00 10^3 c/µL Standard Error 0.016	-0.01 10^3 c/µL Standard Error 0.017	0.00 10^3 c/µL Standard Error 0.011	0.03 10^3 c/µL Standard Error 0.014
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 24 (n=162, 160, 157, 135)	-0.01 10^3 c/µL Standard Error 0.021	-0.03 10^3 c/µL Standard Error 0.022	-0.01 10^3 c/µL Standard Error 0.013	0.01 10^3 c/µL Standard Error 0.011
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 30 (n=159, 155, 154, 136)	-0.01 10^3 c/µL Standard Error 0.018	-0.02 10^3 c/µL Standard Error 0.017	0.00 10^3 c/µL Standard Error 0.012	0.00 10^3 c/µL Standard Error 0.012
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 37 (n=150, 149, 146, 121)	-0.02 10^3 c/µL Standard Error 0.016	-0.00 10^3 c/µL Standard Error 0.037	-0.03 10^3 c/µL Standard Error 0.011	-0.01 10^3 c/µL Standard Error 0.011
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 50 (n=150, 142, 145, 124)	-0.02 10^3 c/µL Standard Error 0.017	-0.03 10^3 c/µL Standard Error 0.021	0.02 10^3 c/µL Standard Error 0.030	-0.02 10^3 c/µL Standard Error 0.011
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 63 (n=147, 136, 140, 115)	-0.02 10^3 c/µL Standard Error 0.018	-0.00 10^3 c/µL Standard Error 0.026	-0.01 10^3 c/µL Standard Error 0.018	-0.01 10^3 c/µL Standard Error 0.015
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 76 (n=134, 126, 130, 94)	-0.01 10^3 c/µL Standard Error 0.020	-0.01 10^3 c/µL Standard Error 0.031	-0.01 10^3 c/µL Standard Error 0.014	-0.03 10^3 c/µL Standard Error 0.015
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 89 (n=122, 113, 123, 85)	-0.05 10^3 c/µL Standard Error 0.023	-0.02 10^3 c/µL Standard Error 0.028	-0.01 10^3 c/µL Standard Error 0.018	-0.03 10^3 c/µL Standard Error 0.015
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 102 (n=104, 104, 111, 68)	0.00 10^3 c/µL Standard Error 0.018	-0.01 10^3 c/µL Standard Error 0.052	0.01 10^3 c/µL Standard Error 0.015	-0.03 10^3 c/µL Standard Error 0.018
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 115 (n=98, 92, 95, 57)	-0.02 10^3 c/µL Standard Error 0.025	0.00 10^3 c/µL Standard Error 0.049	0.00 10^3 c/µL Standard Error 0.013	-0.03 10^3 c/µL Standard Error 0.022
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 128 (n=90, 87, 88, 50)	-0.02 10^3 c/µL Standard Error 0.027	-0.01 10^3 c/µL Standard Error 0.051	0.01 10^3 c/µL Standard Error 0.015	-0.03 10^3 c/µL Standard Error 0.021
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 141 (n=85, 78, 84, 47)	-0.03 10^3 c/µL Standard Error 0.024	-0.01 10^3 c/µL Standard Error 0.032	-0.01 10^3 c/µL Standard Error 0.015	-0.01 10^3 c/µL Standard Error 0.032
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 154 (n=77, 71, 78, 45)	-0.02 10^3 c/µL Standard Error 0.017	-0.01 10^3 c/µL Standard Error 0.051	-0.00 10^3 c/µL Standard Error 0.018	-0.03 10^3 c/µL Standard Error 0.020
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 167 (n=76, 67, 75, 42)	-0.01 10^3 c/µL Standard Error 0.014	0.01 10^3 c/µL Standard Error 0.044	0.00 10^3 c/µL Standard Error 0.020	-0.05 10^3 c/µL Standard Error 0.019
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 180 (n=69, 60, 72, 41)	-0.03 10^3 c/µL Standard Error 0.014	0.03 10^3 c/µL Standard Error 0.044	-0.01 10^3 c/µL Standard Error 0.017	-0.04 10^3 c/µL Standard Error 0.023
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 193 (n=69, 60, 71, 40)	-0.00 10^3 c/µL Standard Error 0.021	-0.02 10^3 c/µL Standard Error 0.020	-0.00 10^3 c/µL Standard Error 0.023	-0.04 10^3 c/µL Standard Error 0.025
Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 206 (n=61, 48, 63, 31)	-0.03 10^3 c/µL Standard Error 0.020	-0.03 10^3 c/µL Standard Error 0.019	0.03 10^3 c/µL Standard Error 0.031	-0.09 10^3 c/µL Standard Error 0.028

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206

Population: Treated participants; n=number of treated participants with measurement at time point

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 2 (n=182, 181, 176, 170)	-2.5 mmHg Standard Error 1.0	-1.6 mmHg Standard Error 1.0	-1.6 mmHg Standard Error 0.9	-3.3 mmHg Standard Error 1.1
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 4 (n=178, 179, 175, 164)	-2.3 mmHg Standard Error 1.1	-2.0 mmHg Standard Error 1.0	-3.3 mmHg Standard Error 0.9	-2.9 mmHg Standard Error 1.1
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 6 (n=178, 176, 171, 162)	-4.1 mmHg Standard Error 1.0	-2.8 mmHg Standard Error 1.1	-2.8 mmHg Standard Error 1.1	-2.8 mmHg Standard Error 1.1
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 8 (n=175, 176, 170, 152)	-4.2 mmHg Standard Error 1.1	-2.9 mmHg Standard Error 1.1	-4.2 mmHg Standard Error 1.1	-3.7 mmHg Standard Error 1.2
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 10 (n=116, 108, 101, 101)	-3.3 mmHg Standard Error 1.2	-2.1 mmHg Standard Error 1.4	-2.8 mmHg Standard Error 1.4	-6.8 mmHg Standard Error 1.5
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 12 (n=170, 166, 161, 138)	-2.8 mmHg Standard Error 1.1	-2.2 mmHg Standard Error 1.1	-4.3 mmHg Standard Error 1.0	-4.3 mmHg Standard Error 1.3
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 14 (n=132, 129, 124, 116)	-2.3 mmHg Standard Error 1.1	-0.7 mmHg Standard Error 1.3	-3.4 mmHg Standard Error 1.1	-2.6 mmHg Standard Error 1.4
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 16 (n=166, 164, 156, 140)	-3.5 mmHg Standard Error 1.1	-2.7 mmHg Standard Error 1.1	-4.4 mmHg Standard Error 1.0	-2.6 mmHg Standard Error 1.2
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 18 (n=144, 141, 132, 123)	-2.2 mmHg Standard Error 1.2	-1.9 mmHg Standard Error 1.2	-4.2 mmHg Standard Error 1.1	-4.1 mmHg Standard Error 1.4
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 20 (n=163, 155, 153, 147)	-2.2 mmHg Standard Error 1.1	-2.9 mmHg Standard Error 1.2	-4.9 mmHg Standard Error 1.2	-4.3 mmHg Standard Error 1.3
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 22 (n=146, 140, 136, 126)	-3.1 mmHg Standard Error 1.2	-2.0 mmHg Standard Error 1.2	-3.1 mmHg Standard Error 1.2	-4.7 mmHg Standard Error 1.3
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 24 (n=165, 160, 161, 140)	-3.6 mmHg Standard Error 1.2	-4.3 mmHg Standard Error 1.2	-3.8 mmHg Standard Error 1.2	-4.5 mmHg Standard Error 1.3
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 30 (n=162, 156, 155, 138)	-1.1 mmHg Standard Error 1.3	-3.6 mmHg Standard Error 1.2	-2.5 mmHg Standard Error 1.2	-3.4 mmHg Standard Error 1.4
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 37 (n=154, 151, 149, 123)	-1.8 mmHg Standard Error 1.3	-2.6 mmHg Standard Error 1.2	-3.3 mmHg Standard Error 1.3	-2.3 mmHg Standard Error 1.2
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 50 (n=155, 147, 151, 130)	-1.7 mmHg Standard Error 1.2	-2.6 mmHg Standard Error 1.3	-1.9 mmHg Standard Error 1.2	-2.9 mmHg Standard Error 1.5
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 63 (n=151, 138, 145, 117)	0.9 mmHg Standard Error 1.2	-0.6 mmHg Standard Error 1.3	-0.6 mmHg Standard Error 1.3	-0.0 mmHg Standard Error 1.3
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 76 (n=134, 126, 133, 98)	-0.6 mmHg Standard Error 1.4	-0.1 mmHg Standard Error 1.5	-0.7 mmHg Standard Error 1.3	-1.7 mmHg Standard Error 1.6
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 89 (n=124, 117, 125, 86)	0.3 mmHg Standard Error 1.4	-3.7 mmHg Standard Error 1.3	-1.7 mmHg Standard Error 1.4	0.3 mmHg Standard Error 1.6
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 102 (n=111, 107, 113, 73)	0.6 mmHg Standard Error 1.5	-3.2 mmHg Standard Error 1.5	-2.8 mmHg Standard Error 1.4	-2.0 mmHg Standard Error 2.0
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 115 (n=100, 94, 98, 58)	2.0 mmHg Standard Error 1.8	-0.4 mmHg Standard Error 1.8	-1.3 mmHg Standard Error 1.6	-2.8 mmHg Standard Error 1.9
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 128 (n=94, 88, 90, 52)	2.9 mmHg Standard Error 2.0	-0.4 mmHg Standard Error 1.7	1.5 mmHg Standard Error 1.7	-2.5 mmHg Standard Error 2.0
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 141 (n=87, 82, 85, 49)	2.0 mmHg Standard Error 1.6	-0.7 mmHg Standard Error 1.8	-1.5 mmHg Standard Error 1.7	0.3 mmHg Standard Error 2.3
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 154 (n=84, 75, 79, 45)	-0.0 mmHg Standard Error 1.8	0.3 mmHg Standard Error 1.7	1.5 mmHg Standard Error 1.8	-2.8 mmHg Standard Error 2.3
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 167 (n=78, 67, 75, 42)	-0.4 mmHg Standard Error 2.1	0.8 mmHg Standard Error 1.7	0.7 mmHg Standard Error 1.7	-1.8 mmHg Standard Error 2.5
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 180 (n=71, 63, 74, 41)	3.1 mmHg Standard Error 2.1	-0.0 mmHg Standard Error 2.0	3.5 mmHg Standard Error 1.7	2.7 mmHg Standard Error 2.5
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 193 (n=70, 60, 72, 40)	0.9 mmHg Standard Error 2.3	-0.1 mmHg Standard Error 2.0	0.2 mmHg Standard Error 1.8	-1.4 mmHg Standard Error 2.4
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period Change from BL at Week 206 (n=61, 53, 64, 33)	2.2 mmHg Standard Error 2.3	-2.6 mmHg Standard Error 2.1	1.7 mmHg Standard Error 1.9	-0.4 mmHg Standard Error 2.2

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206

Population: Treated participants; n=number of treated participants with measurement at time point

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 2 (n=182, 181, 176, 170)	-1.1 mmHg Standard Error 0.7	-1.0 mmHg Standard Error 0.6	-0.9 mmHg Standard Error 0.6	-1.5 mmHg Standard Error 0.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 4 (n=178, 179, 175, 164)	-0.9 mmHg Standard Error 0.7	-0.3 mmHg Standard Error 0.7	-1.3 mmHg Standard Error 0.6	-1.4 mmHg Standard Error 0.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 6 (n=178, 176, 171, 162)	-1.6 mmHg Standard Error 0.7	-0.1 mmHg Standard Error 0.7	-0.5 mmHg Standard Error 0.6	-1.4 mmHg Standard Error 0.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 8 (n=175, 176, 170, 152)	-1.9 mmHg Standard Error 0.7	-1.1 mmHg Standard Error 0.7	-1.5 mmHg Standard Error 0.6	-2.2 mmHg Standard Error 0.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 10 (n=116, 108, 101, 101)	-0.5 mmHg Standard Error 0.8	0.3 mmHg Standard Error 0.8	-1.6 mmHg Standard Error 0.8	-3.4 mmHg Standard Error 0.9
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 12 (n=170, 166, 161, 138)	-1.0 mmHg Standard Error 0.7	-0.6 mmHg Standard Error 0.7	-2.1 mmHg Standard Error 0.6	-1.7 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 14 (n=132, 129, 124, 116)	-0.4 mmHg Standard Error 0.7	-0.2 mmHg Standard Error 0.8	-2.2 mmHg Standard Error 0.7	-2.1 mmHg Standard Error 0.9
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 16 (n=166, 164, 156, 140)	-1.0 mmHg Standard Error 0.6	-0.7 mmHg Standard Error 0.7	-1.7 mmHg Standard Error 0.6	-1.0 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 18 (n=144, 141, 132, 123)	-0.7 mmHg Standard Error 0.8	-1.4 mmHg Standard Error 0.8	-2.3 mmHg Standard Error 0.7	-1.8 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 20 (n=163, 155, 153, 147)	-1.0 mmHg Standard Error 0.7	-1.2 mmHg Standard Error 0.7	-2.1 mmHg Standard Error 0.7	-1.9 mmHg Standard Error 0.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 22 (n=146, 140, 136, 126)	-1.2 mmHg Standard Error 0.8	-0.7 mmHg Standard Error 0.8	-1.6 mmHg Standard Error 0.8	-1.6 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 24 (n=165, 160, 161, 140)	-1.3 mmHg Standard Error 0.8	-1.3 mmHg Standard Error 0.7	-2.5 mmHg Standard Error 0.7	-2.4 mmHg Standard Error 0.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 30 (n=162, 156, 155, 138)	-0.5 mmHg Standard Error 0.8	-0.9 mmHg Standard Error 0.8	-1.6 mmHg Standard Error 0.7	-1.6 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 37 (n=154, 151, 149, 123)	-1.1 mmHg Standard Error 0.8	-0.9 mmHg Standard Error 0.7	-1.9 mmHg Standard Error 0.8	-1.6 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 50 (n=155, 147, 151, 130)	-1.7 mmHg Standard Error 0.8	-1.1 mmHg Standard Error 0.8	-1.5 mmHg Standard Error 0.7	-1.4 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 63 (n=151, 138, 145, 117)	-0.3 mmHg Standard Error 0.7	-0.8 mmHg Standard Error 0.8	-0.9 mmHg Standard Error 0.7	-0.7 mmHg Standard Error 0.8
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 76 (n=134, 126, 133, 98)	-1.2 mmHg Standard Error 0.8	-0.2 mmHg Standard Error 0.9	-1.6 mmHg Standard Error 0.8	-1.8 mmHg Standard Error 1.0
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 89 (n=124, 117, 125, 86)	-0.8 mmHg Standard Error 0.8	-1.2 mmHg Standard Error 0.8	-1.9 mmHg Standard Error 0.8	-2.1 mmHg Standard Error 1.0
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 102 (n=111, 107, 113, 73)	-0.4 mmHg Standard Error 1.0	-2.2 mmHg Standard Error 0.9	-2.3 mmHg Standard Error 0.9	-3.6 mmHg Standard Error 1.2
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 115 (n=100, 94, 98, 58)	0.7 mmHg Standard Error 1.1	-0.1 mmHg Standard Error 1.0	-1.1 mmHg Standard Error 1.1	-3.6 mmHg Standard Error 1.2
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 128 (n=94, 88, 90, 52)	0.0 mmHg Standard Error 1.1	-0.6 mmHg Standard Error 1.1	-1.2 mmHg Standard Error 1.0	-3.1 mmHg Standard Error 1.3
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 141 (n=87, 82, 85, 49)	0.3 mmHg Standard Error 1.1	0.7 mmHg Standard Error 1.1	-3.0 mmHg Standard Error 1.1	-2.7 mmHg Standard Error 1.5
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 154 (n=84, 75, 79, 45)	-1.8 mmHg Standard Error 1.1	-0.7 mmHg Standard Error 1.0	-2.7 mmHg Standard Error 1.1	-4.6 mmHg Standard Error 1.2
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 167 (n=78, 67, 75, 42)	-1.4 mmHg Standard Error 1.3	2.1 mmHg Standard Error 1.0	-1.6 mmHg Standard Error 1.2	-2.0 mmHg Standard Error 1.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 180 (n=71, 63, 74, 41)	-1.4 mmHg Standard Error 1.2	-0.3 mmHg Standard Error 0.9	-0.9 mmHg Standard Error 1.2	-1.6 mmHg Standard Error 1.7
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 193 (n=70, 60, 72, 40)	-2.6 mmHg Standard Error 1.3	0.4 mmHg Standard Error 1.2	-1.7 mmHg Standard Error 1.2	-2.6 mmHg Standard Error 1.6
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period Change from BL at Week 206 (n=61, 53, 64, 33)	-0.6 mmHg Standard Error 1.4	-2.8 mmHg Standard Error 1.0	-2.3 mmHg Standard Error 1.3	-2.8 mmHg Standard Error 1.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206

Population: Treated participants; n=number of treated participants with measurement at time point

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 141 (n=87, 82, 85, 49)	-1.7 beats/min Standard Error 1.2	-1.7 beats/min Standard Error 1.0	-0.6 beats/min Standard Error 1.2	-1.2 beats/min Standard Error 1.3
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 2 (n=182, 181, 176, 170)	1.0 beats/min Standard Error 0.7	-0.3 beats/min Standard Error 0.7	-0.4 beats/min Standard Error 0.8	0.7 beats/min Standard Error 0.7
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 4 (n=178, 179, 175, 164)	1.3 beats/min Standard Error 0.6	-0.1 beats/min Standard Error 0.8	-0.0 beats/min Standard Error 0.7	0.1 beats/min Standard Error 0.6
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 6 (n=178, 176, 171, 162)	1.0 beats/min Standard Error 0.6	-0.2 beats/min Standard Error 0.7	-0.2 beats/min Standard Error 0.7	-0.5 beats/min Standard Error 0.7
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 8 (n=175, 176, 170, 152)	0.8 beats/min Standard Error 0.6	0.5 beats/min Standard Error 0.7	0.6 beats/min Standard Error 0.7	-0.6 beats/min Standard Error 0.7
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 10 (n=116, 106, 100, 101)	0.9 beats/min Standard Error 0.8	-0.5 beats/min Standard Error 0.8	0.2 beats/min Standard Error 1.0	-1.5 beats/min Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 12 (n=170, 166, 161, 138)	0.7 beats/min Standard Error 0.6	-0.2 beats/min Standard Error 0.7	0.1 beats/min Standard Error 0.7	-1.5 beats/min Standard Error 0.8
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 14 (n=132, 129, 124, 116)	1.4 beats/min Standard Error 0.8	-0.1 beats/min Standard Error 0.8	1.0 beats/min Standard Error 0.9	-1.5 beats/min Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 16 (n=166, 164, 156, 140)	0.4 beats/min Standard Error 0.7	-0.6 beats/min Standard Error 0.7	-0.5 beats/min Standard Error 0.8	-0.5 beats/min Standard Error 0.8
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 18 (n=144, 141, 132, 123)	1.6 beats/min Standard Error 0.8	-0.0 beats/min Standard Error 0.8	0.3 beats/min Standard Error 0.8	-0.5 beats/min Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 20 (n=163, 155, 153, 147)	0.9 beats/min Standard Error 0.7	-0.0 beats/min Standard Error 0.7	-0.3 beats/min Standard Error 0.8	-0.8 beats/min Standard Error 0.8
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 22 (n=146, 140, 136, 126)	2.4 beats/min Standard Error 0.8	0.4 beats/min Standard Error 0.9	0.3 beats/min Standard Error 0.8	-1.6 beats/min Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 24 (n=165, 160, 161, 140)	0.2 beats/min Standard Error 0.7	-0.6 beats/min Standard Error 0.8	0.4 beats/min Standard Error 0.7	-0.7 beats/min Standard Error 0.7
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 30 (n=162, 156, 154, 138)	0.5 beats/min Standard Error 0.7	-0.7 beats/min Standard Error 0.8	-0.3 beats/min Standard Error 0.8	-0.1 beats/min Standard Error 0.8
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 37 (n=154, 151, 149, 123)	0.6 beats/min Standard Error 0.7	-1.2 beats/min Standard Error 0.8	-0.3 beats/min Standard Error 0.8	-0.6 beats/min Standard Error 0.8
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 50 (n=154, 147, 151, 130)	0.8 beats/min Standard Error 0.8	-1.0 beats/min Standard Error 0.8	0.1 beats/min Standard Error 0.8	-1.0 beats/min Standard Error 0.8
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 63 (n=151, 138, 145, 117)	0.4 beats/min Standard Error 0.8	-0.8 beats/min Standard Error 0.8	-0.8 beats/min Standard Error 0.7	-0.5 beats/min Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 76 (n=134, 126, 133, 98)	-0.0 beats/min Standard Error 0.9	-1.3 beats/min Standard Error 0.8	-0.5 beats/min Standard Error 0.9	-1.4 beats/min Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 89 (n=124, 116, 125, 86)	-0.3 beats/min Standard Error 0.9	-1.5 beats/min Standard Error 0.8	-0.2 beats/min Standard Error 0.8	-1.6 beats/min Standard Error 1.0
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 102 (n=111, 107, 113, 73)	0.5 beats/min Standard Error 0.9	-0.6 beats/min Standard Error 0.9	0.6 beats/min Standard Error 0.8	-1.8 beats/min Standard Error 1.2
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 115 (n=100, 94, 98, 58)	-0.3 beats/min Standard Error 1.1	-0.5 beats/min Standard Error 0.9	-0.8 beats/min Standard Error 1.0	-2.4 beats/min Standard Error 1.2
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 128 (n=94, 88, 90, 52)	-0.7 beats/min Standard Error 1.2	-0.2 beats/min Standard Error 0.9	-0.9 beats/min Standard Error 1.1	-0.9 beats/min Standard Error 1.3
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 154 (n=84, 75, 79, 45)	-0.9 beats/min Standard Error 1.4	-0.6 beats/min Standard Error 0.9	-0.0 beats/min Standard Error 1.2	-2.8 beats/min Standard Error 1.4
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 167 (n=78, 67, 75, 42)	-0.0 beats/min Standard Error 1.3	0.3 beats/min Standard Error 1.0	-1.2 beats/min Standard Error 1.2	-0.9 beats/min Standard Error 1.4
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 180 (n=71, 63, 74, 41)	-2.8 beats/min Standard Error 1.3	-0.8 beats/min Standard Error 1.1	0.2 beats/min Standard Error 1.6	-2.7 beats/min Standard Error 1.3
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 193 (n=70, 60, 72, 40)	-2.2 beats/min Standard Error 1.3	-0.3 beats/min Standard Error 1.1	-1.1 beats/min Standard Error 1.1	-1.8 beats/min Standard Error 1.5
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 206 (n=61, 53, 64, 33)	-0.9 beats/min Standard Error 1.2	0.1 beats/min Standard Error 1.2	-1.2 beats/min Standard Error 1.2	-1.1 beats/min Standard Error 1.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 12, 24, 76, 102, 154, 206,

Population: Number of Participants Analyzed=Treated Participants; BL n=normal or abnormal ECG status at baseline of the cohort of participants with measure at given time point

The normality/abnormality of the ECG tracing was determined by the investigator.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 12(BL n=108, 109, 104, 104)	98 participants	97 participants	94 participants	82 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 12 (BL n=108,109,104,104)	11 participants	11 participants	10 participants	22 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 12 (BL n=69, 66, 70, 58)	22 participants	14 participants	22 participants	12 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 12(BL n=69, 66, 70, 58)	44 participants	55 participants	48 participants	46 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 24 (BL n=96, 87, 83, 77)	79 participants	82 participants	70 participants	61 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 24 (BL n=96, 87, 83, 77)	8 participants	14 participants	13 participants	16 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 24 (BL n=58, 58, 56, 41)	22 participants	16 participants	15 participants	14 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 24(BL n=58, 58, 56, 41)	36 participants	42 participants	41 participants	27 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 76 (BL n=94, 89, 92, 81)	74 participants	75 participants	73 participants	60 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 76 (BL n=94, 89, 92, 81)	15 participants	19 participants	19 participants	21 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 76 (BL n=51, 52, 59, 44)	18 participants	13 participants	18 participants	13 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 76 (BL n=51,52,59,44)	34 participants	38 participants	41 participants	31 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 102 (BL n=80, 66, 65, 50)	55 participants	63 participants	48 participants	41 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 102 (BL n=80, 66, 65, 50)	11 participants	17 participants	17 participants	9 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 102 (BL n=43,45,49, 21)	14 participants	11 participants	14 participants	6 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 102 (BL n=43,45,49, 21)	31 participants	32 participants	35 participants	15 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 154 (BL n=60, 46, 53, 34)	36 participants	48 participants	37 participants	26 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 154 (BL n=60, 46, 53, 34)	10 participants	12 participants	16 participants	8 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 154 (BL n=26, 34, 34, 16)	13 participants	10 participants	12 participants	7 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 154 (BL n=26,34,34,16)	21 participants	16 participants	22 participants	9 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 206 (BL n=48, 31, 42, 24)	27 participants	39 participants	32 participants	16 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 206 (BL n=48, 31, 42, 24)	4 participants	9 participants	10 participants	8 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 206 (BL n=20, 25, 28, 13)	9 participants	9 participants	11 participants	7 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 206 (BL n=20,25,28,13)	16 participants	11 participants	17 participants	6 participants

OTHER_PRE_SPECIFIED outcome

Population: Treated participants

Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which are hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
All Reported Hypoglycemic Adverse Events During the ST + LT Treatment Period	20 participants	23 participants	21 participants	20 participants

OTHER_PRE_SPECIFIED outcome

Population: Treated participants

'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick glucose \<= 50 mg/dL and associated symptoms.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Confirmed Hypoglycemia During the ST + LT Treatment Period	2 participants	3 participants	3 participants	1 participants

Adverse Events

Placebo+ Metformin

Serious events: 15 serious events

Other events: 129 other events

Deaths: 0 deaths

Saxagliptin 10 mg + Metformin

Serious events: 22 serious events

Other events: 133 other events

Deaths: 0 deaths

Saxagliptin 2.5 mg + Metformin

Serious events: 23 serious events

Other events: 139 other events

Deaths: 0 deaths

Saxagliptin 5 mg + Metformin

Serious events: 27 serious events

Other events: 133 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo+ Metformin n=179 participants at risk Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 participants at risk Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 participants at risk Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 5 mg + Metformin n=191 participants at risk Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Hepatobiliary disorders CHOLECYSTITIS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.52% 1/191
Hepatobiliary disorders CHOLELITHIASIS	0.56% 1/179	0.55% 1/181	0.52% 1/192	0.00% 0/191
Infections and infestations PYELONEPHRITIS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Blood and lymphatic system disorders ANAEMIA	0.00% 0/179	1.1% 2/181	0.52% 1/192	0.00% 0/191
Metabolism and nutrition disorders DEHYDRATION	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Hepatobiliary disorders BILIARY COLIC	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Cardiac disorders CORONARY ARTERY INSUFFICIENCY	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Cardiac disorders MYOCARDIAL INFARCTION	1.7% 3/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Cardiac disorders CORONARY ARTERY DISEASE	0.00% 0/179	1.1% 2/181	0.00% 0/192	2.1% 4/191
Cardiac disorders CARDIAC FAILURE CONGESTIVE	1.1% 2/179	0.00% 0/181	0.00% 0/192	1.6% 3/191
Cardiac disorders SUPRAVENTRICULAR TACHYCARDIA	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Vascular disorders VARICOSE VEIN	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Vascular disorders HYPERTENSIVE CRISIS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Psychiatric disorders DEPRESSION	0.56% 1/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Psychiatric disorders MAJOR DEPRESSION	0.56% 1/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Psychiatric disorders PSYCHIATRIC SYMPTOM	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.00% 0/179	0.55% 1/181	0.52% 1/192	0.00% 0/191
Immune system disorders SARCOIDOSIS	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Immune system disorders DRUG HYPERSENSITIVITY	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Nervous system disorders HEADACHE	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Nervous system disorders DIZZINESS	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Nervous system disorders SOMNOLENCE	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.00% 0/179	1.7% 3/181	0.52% 1/192	0.00% 0/191
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Nervous system disorders ALTERED STATE OF CONSCIOUSNESS	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Gastrointestinal disorders VOMITING	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Gastrointestinal disorders DIARRHOEA	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Gastrointestinal disorders FOOD POISONING	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Gastrointestinal disorders ABDOMINAL HERNIA	0.00% 0/179	0.55% 1/181	0.52% 1/192	0.00% 0/191
Gastrointestinal disorders STOMACH GRANULOMA	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Gastrointestinal disorders INTESTINAL OBSTRUCTION	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations PNEUMONIA	0.56% 1/179	0.00% 0/181	1.0% 2/192	0.52% 1/191
Infections and infestations SINUSITIS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Infections and infestations UROSEPSIS	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Infections and infestations CELLULITIS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations ERYSIPELAS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Infections and infestations APPENDICITIS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations BREAST ABSCESS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations DIVERTICULITIS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.52% 1/191
Infections and infestations SCROTAL ABSCESS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations SINUSITIS BACTERIAL	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations PERIUMBILICAL ABSCESS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations MENINGITIS TUBERCULOUS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Infections and infestations APPENDICITIS PERFORATED	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Infections and infestations URINARY TRACT INFECTION	0.00% 0/179	0.55% 1/181	0.52% 1/192	0.00% 0/191
Infections and infestations CLOSTRIDIUM DIFFICILE COLITIS	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Renal and urinary disorders NEPHROLITHIASIS	0.56% 1/179	0.55% 1/181	0.00% 0/192	0.52% 1/191
Renal and urinary disorders CALCULUS URINARY	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Renal and urinary disorders CALCULUS URETERIC	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Renal and urinary disorders RENAL FAILURE ACUTE	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Surgical and medical procedures STERILISATION	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Reproductive system and breast disorders CYSTOCELE	0.56% 1/179	0.00% 0/181	0.00% 0/192	0.00% 0/191
Reproductive system and breast disorders RECTOCELE	0.56% 1/179	0.00% 0/181	0.00% 0/192	0.00% 0/191
Reproductive system and breast disorders PROSTATITIS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Reproductive system and breast disorders DYSFUNCTIONAL UTERINE BLEEDING	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Injury, poisoning and procedural complications FALL	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Injury, poisoning and procedural complications LIMB INJURY	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Injury, poisoning and procedural complications HIP FRACTURE	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Injury, poisoning and procedural complications ANKLE FRACTURE	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.52% 1/191
Injury, poisoning and procedural complications SKIN LACERATION	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Injury, poisoning and procedural complications INCISIONAL HERNIA	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.52% 1/191
Injury, poisoning and procedural complications UPPER LIMB FRACTURE	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Injury, poisoning and procedural complications ROAD TRAFFIC ACCIDENT	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Musculoskeletal and connective tissue disorders EXOSTOSIS	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.52% 1/191
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.56% 1/179	0.00% 0/181	0.00% 0/192	0.00% 0/191
Musculoskeletal and connective tissue disorders RHEUMATOID ARTHRITIS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Respiratory, thoracic and mediastinal disorders ASTHMA	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.52% 1/191
General disorders HERNIA	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
General disorders CHEST PAIN	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
General disorders PELVIC MASS	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEURILEMMOMA	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) UTERINE CANCER	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	0.00% 0/179	0.55% 1/181	0.52% 1/192	0.00% 0/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MULTIPLE MYELOMA	0.00% 0/179	0.00% 0/181	0.00% 0/192	0.52% 1/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BASAL CELL CARCINOMA	0.56% 1/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NON-HODGKIN'S LYMPHOMA	0.00% 0/179	0.00% 0/181	0.52% 1/192	0.00% 0/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER RECURRENT	0.56% 1/179	0.00% 0/181	0.00% 0/192	0.00% 0/191
Neoplasms benign, malignant and unspecified (incl cysts and polyps) GASTROINTESTINAL CARCINOMA	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191
Cardiac disorders ANGINA PECTORIS	0.56% 1/179	0.00% 0/181	0.00% 0/192	0.00% 0/191
Cardiac disorders ANGINA UNSTABLE	0.56% 1/179	0.00% 0/181	0.00% 0/192	0.00% 0/191
Cardiac disorders CARDIOGENIC SHOCK	0.56% 1/179	0.00% 0/181	0.00% 0/192	0.00% 0/191
Cardiac disorders MYOCARDIAL ISCHAEMIA	0.00% 0/179	0.55% 1/181	0.00% 0/192	0.00% 0/191

Other adverse events

Other adverse events
Measure	Placebo+ Metformin n=179 participants at risk Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 participants at risk Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 participants at risk Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 5 mg + Metformin n=191 participants at risk Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Infections and infestations INFLUENZA	15.1% 27/179	15.5% 28/181	14.1% 27/192	16.2% 31/191
Infections and infestations SINUSITIS	4.5% 8/179	8.3% 15/181	4.7% 9/192	7.3% 14/191
Infections and infestations BRONCHITIS	7.3% 13/179	6.6% 12/181	7.8% 15/192	9.9% 19/191
Infections and infestations GASTROENTERITIS	2.2% 4/179	2.8% 5/181	5.2% 10/192	3.1% 6/191
Infections and infestations NASOPHARYNGITIS	14.0% 25/179	15.5% 28/181	14.6% 28/192	14.7% 28/191
Infections and infestations URINARY TRACT INFECTION	8.4% 15/179	12.2% 22/181	13.5% 26/192	8.4% 16/191
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	9.5% 17/179	11.6% 21/181	13.0% 25/192	9.9% 19/191
Blood and lymphatic system disorders ANAEMIA	2.2% 4/179	2.8% 5/181	3.6% 7/192	7.9% 15/191
Skin and subcutaneous tissue disorders RASH	2.8% 5/179	6.6% 12/181	2.6% 5/192	3.1% 6/191
Musculoskeletal and connective tissue disorders MYALGIA	1.7% 3/179	4.4% 8/181	5.2% 10/192	3.7% 7/191
Musculoskeletal and connective tissue disorders BACK PAIN	10.6% 19/179	7.7% 14/181	9.9% 19/192	8.4% 16/191
Musculoskeletal and connective tissue disorders ARTHRALGIA	6.7% 12/179	12.7% 23/181	11.5% 22/192	10.5% 20/191
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	9.5% 17/179	8.3% 15/181	7.3% 14/192	5.2% 10/191
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	5.0% 9/179	5.5% 10/181	2.6% 5/192	2.6% 5/191
Respiratory, thoracic and mediastinal disorders COUGH	6.1% 11/179	5.0% 9/181	7.8% 15/192	4.7% 9/191
General disorders OEDEMA PERIPHERAL	6.7% 12/179	8.8% 16/181	8.3% 16/192	7.9% 15/191
Nervous system disorders HEADACHE	12.3% 22/179	13.3% 24/181	14.1% 27/192	9.4% 18/191
Nervous system disorders DIZZINESS	5.6% 10/179	4.4% 8/181	4.7% 9/192	4.2% 8/191
Gastrointestinal disorders NAUSEA	4.5% 8/179	7.7% 14/181	5.7% 11/192	3.7% 7/191
Gastrointestinal disorders VOMITING	4.5% 8/179	3.9% 7/181	6.2% 12/192	4.7% 9/191
Gastrointestinal disorders DIARRHOEA	12.8% 23/179	10.5% 19/181	15.1% 29/192	9.9% 19/191
Gastrointestinal disorders DYSPEPSIA	4.5% 8/179	3.3% 6/181	4.7% 9/192	6.3% 12/191
Gastrointestinal disorders GASTRITIS	1.1% 2/179	2.2% 4/181	5.2% 10/192	1.6% 3/191
Gastrointestinal disorders TOOTHACHE	6.1% 11/179	1.1% 2/181	3.1% 6/192	5.2% 10/191
Gastrointestinal disorders ABDOMINAL PAIN	1.7% 3/179	2.8% 5/181	6.8% 13/192	4.2% 8/191
Gastrointestinal disorders ABDOMINAL PAIN UPPER	2.8% 5/179	3.3% 6/181	3.1% 6/192	5.2% 10/191
Vascular disorders HYPERTENSION	7.3% 13/179	8.8% 16/181	10.9% 21/192	7.3% 14/191

Additional Information

Boaz Hirschberg

AstraZeneca Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Baseline (Week 0) (n=192, 191, 181, 179)	42.3 percentage red blood cells Standard Error 0.25	41.9 percentage red blood cells Standard Error 0.26	42.2 percentage red blood cells Standard Error 0.29	41.8 percentage red blood cells Standard Error 0.28
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 2 (n=181, 177, 172, 169)	-0.5 percentage red blood cells Standard Error 0.17	-0.3 percentage red blood cells Standard Error 0.15	-0.5 percentage red blood cells Standard Error 0.15	-0.4 percentage red blood cells Standard Error 0.15
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 4 (n=178, 178, 174, 166)	-0.4 percentage red blood cells Standard Error 0.15	-0.3 percentage red blood cells Standard Error 0.17	-0.2 percentage red blood cells Standard Error 0.18	-0.0 percentage red blood cells Standard Error 0.17
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 6 (n=176, 174, 166, 160)	-0.3 percentage red blood cells Standard Error 0.17	-0.2 percentage red blood cells Standard Error 0.17	-0.1 percentage red blood cells Standard Error 0.18	-0.0 percentage red blood cells Standard Error 0.17
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 141 (n=85, 79, 85, 48)	-0.6 percentage red blood cells Standard Error 0.28	-0.6 percentage red blood cells Standard Error 0.26	-0.3 percentage red blood cells Standard Error 0.31	-0.9 percentage red blood cells Standard Error 0.37
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 154 (n=81, 74, 78, 45)	-1.7 percentage red blood cells Standard Error 0.30	-1.5 percentage red blood cells Standard Error 0.28	-1.2 percentage red blood cells Standard Error 0.32	-1.6 percentage red blood cells Standard Error 0.34
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 8 (n=173, 176, 165, 157)	-0.1 percentage red blood cells Standard Error 0.17	-0.4 percentage red blood cells Standard Error 0.18	-0.0 percentage red blood cells Standard Error 0.19	-0.0 percentage red blood cells Standard Error 0.19
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 10 (n=149, 134, 137, 131)	-0.4 percentage red blood cells Standard Error 0.18	-0.4 percentage red blood cells Standard Error 0.19	-0.2 percentage red blood cells Standard Error 0.21	-0.1 percentage red blood cells Standard Error 0.20
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 12 (n=170, 167, 160, 144)	-0.1 percentage red blood cells Standard Error 0.17	-0.1 percentage red blood cells Standard Error 0.18	0.4 percentage red blood cells Standard Error 0.19	0.0 percentage red blood cells Standard Error 0.20
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 14 (n=156, 154, 146, 139)	-0.2 percentage red blood cells Standard Error 0.17	-0.2 percentage red blood cells Standard Error 0.18	-0.1 percentage red blood cells Standard Error 0.23	0.0 percentage red blood cells Standard Error 0.20
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 16 (n=167, 166, 159, 140)	0.0 percentage red blood cells Standard Error 0.18	-0.1 percentage red blood cells Standard Error 0.20	-0.1 percentage red blood cells Standard Error 0.21	0.2 percentage red blood cells Standard Error 0.19
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 18 (n=155, 158, 149, 141)	-0.5 percentage red blood cells Standard Error 0.17	-0.3 percentage red blood cells Standard Error 0.21	-0.3 percentage red blood cells Standard Error 0.18	-0.1 percentage red blood cells Standard Error 0.21
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 20 (n=162, 153, 154, 147)	-0.3 percentage red blood cells Standard Error 0.19	-0.1 percentage red blood cells Standard Error 0.19	-0.2 percentage red blood cells Standard Error 0.20	-0.3 percentage red blood cells Standard Error 0.20
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 22 (n=157, 152, 143, 138)	-0.5 percentage red blood cells Standard Error 0.21	-0.2 percentage red blood cells Standard Error 0.21	-0.5 percentage red blood cells Standard Error 0.21	-0.5 percentage red blood cells Standard Error 0.23
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 24 (n=164, 160, 159, 137)	-0.4 percentage red blood cells Standard Error 0.21	-0.3 percentage red blood cells Standard Error 0.20	-0.3 percentage red blood cells Standard Error 0.19	-0.4 percentage red blood cells Standard Error 0.22
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 30 (n=161, 155, 154, 137)	-0.4 percentage red blood cells Standard Error 0.23	-0.2 percentage red blood cells Standard Error 0.19	-0.0 percentage red blood cells Standard Error 0.21	-0.2 percentage red blood cells Standard Error 0.23
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 37 (n=152, 149, 146, 122)	-0.4 percentage red blood cells Standard Error 0.21	-0.1 percentage red blood cells Standard Error 0.21	0.0 percentage red blood cells Standard Error 0.23	-0.1 percentage red blood cells Standard Error 0.21
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 50 (n=151, 142, 146, 127)	-0.5 percentage red blood cells Standard Error 0.23	-0.4 percentage red blood cells Standard Error 0.21	-0.1 percentage red blood cells Standard Error 0.22	-0.0 percentage red blood cells Standard Error 0.25
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 63 (n=148, 137, 142, 116)	-0.5 percentage red blood cells Standard Error 0.28	0.1 percentage red blood cells Standard Error 0.22	-0.1 percentage red blood cells Standard Error 0.22	-0.0 percentage red blood cells Standard Error 0.24
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 76 (n=134, 126, 130, 94)	-0.4 percentage red blood cells Standard Error 0.23	-0.2 percentage red blood cells Standard Error 0.25	0.1 percentage red blood cells Standard Error 0.22	-0.4 percentage red blood cells Standard Error 0.28
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 89 (n=123, 114, 123, 85)	-0.5 percentage red blood cells Standard Error 0.25	-0.2 percentage red blood cells Standard Error 0.27	-0.3 percentage red blood cells Standard Error 0.27	-0.3 percentage red blood cells Standard Error 0.29
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 102 (n=108, 104, 112, 70)	-0.9 percentage red blood cells Standard Error 0.29	-0.7 percentage red blood cells Standard Error 0.21	-0.2 percentage red blood cells Standard Error 0.25	-0.7 percentage red blood cells Standard Error 0.31
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 115 (n=99, 94, 98, 58)	0.0 percentage red blood cells Standard Error 0.29	-0.1 percentage red blood cells Standard Error 0.22	-0.4 percentage red blood cells Standard Error 0.28	-0.2 percentage red blood cells Standard Error 0.33
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 128 (n=92, 88, 90, 52)	-0.5 percentage red blood cells Standard Error 0.32	-0.6 percentage red blood cells Standard Error 0.27	-0.5 percentage red blood cells Standard Error 0.28	-0.5 percentage red blood cells Standard Error 0.34
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 167 (n=77, 67, 75, 42)	-1.6 percentage red blood cells Standard Error 0.34	-1.0 percentage red blood cells Standard Error 0.26	-1.2 percentage red blood cells Standard Error 0.36	-1.1 percentage red blood cells Standard Error 0.41
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 180 (n=70, 61, 73, 41)	-1.8 percentage red blood cells Standard Error 0.46	-1.1 percentage red blood cells Standard Error 0.32	-0.7 percentage red blood cells Standard Error 0.30	-1.2 percentage red blood cells Standard Error 0.34
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 193 (n=70, 60, 72, 40)	-1.7 percentage red blood cells Standard Error 0.46	-0.7 percentage red blood cells Standard Error 0.33	-0.5 percentage red blood cells Standard Error 0.33	-0.7 percentage red blood cells Standard Error 0.42
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 206 (n=61, 50, 64, 31)	-2.3 percentage red blood cells Standard Error 0.41	-1.5 percentage red blood cells Standard Error 0.35	-0.7 percentage red blood cells Standard Error 0.32	-1.3 percentage red blood cells Standard Error 0.48

Measure	Saxagliptin 5 mg + Metformin n=191 Participants Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 2.5 mg + Metformin n=192 Participants Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Saxagliptin 10 mg + Metformin n=181 Participants Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).	Placebo+ Metformin n=179 Participants Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 2 (n=178, 175, 170, 169)	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.002	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 4 (n=176, 175, 170, 166)	-0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.004	-0.00 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 8 (n=172, 172, 163, 153)	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 10 (n=148, 130, 137, 128)	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.004
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 12 (n=168, 166, 159, 141)	0.00 10^3 c/µL Standard Error 0.004	0.00 10^3 c/µL Standard Error 0.004	-0.00 10^3 c/µL Standard Error 0.003	-0.01 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 14 (n=156, 152, 145, 136)	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	-0.01 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 16 (n=166, 166, 157, 137)	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 18 (n=155, 157, 149, 139)	0.00 10^3 c/µL Standard Error 0.004	0.00 10^3 c/µL Standard Error 0.004	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 20 (n=162, 153, 154, 146)	-0.01 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.004
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 22 (n=157, 151, 143, 138)	0.00 10^3 c/µL Standard Error 0.004	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.005
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 24 (n=162, 160, 157, 135)	0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.004	0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.004
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 30 (n=159, 155, 154, 136)	0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.004	0.00 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 37 (n=150, 149, 146, 121)	0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.003	0.01 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.004
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 50 (n=150, 142, 145, 124)	0.01 10^3 c/µL Standard Error 0.004	0.01 10^3 c/µL Standard Error 0.003	0.01 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.004
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 6 (n=175, 172, 165, 158)	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	-0.00 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.004
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Baseline (Week 0) (n=192, 191, 181, 179)	0.02 10^3 c/µL Standard Error 0.003	0.02 10^3 c/µL Standard Error 0.003	0.02 10^3 c/µL Standard Error 0.003	0.02 10^3 c/µL Standard Error 0.003
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 63 (n=147, 136, 140, 115)	0.01 10^3 c/µL Standard Error 0.004	0.01 10^3 c/µL Standard Error 0.004	0.01 10^3 c/µL Standard Error 0.005	0.00 10^3 c/µL Standard Error 0.004
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 76 (n=134, 126, 130, 94)	0.01 10^3 c/µL Standard Error 0.004	0.02 10^3 c/µL Standard Error 0.005	0.02 10^3 c/µL Standard Error 0.005	0.00 10^3 c/µL Standard Error 0.005
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 89 (n=122, 113, 123, 85)	0.01 10^3 c/µL Standard Error 0.004	0.01 10^3 c/µL Standard Error 0.004	0.01 10^3 c/µL Standard Error 0.003	0.00 10^3 c/µL Standard Error 0.005
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 102 (n=104, 104, 111, 68)	0.01 10^3 c/µL Standard Error 0.005	0.01 10^3 c/µL Standard Error 0.005	0.02 10^3 c/µL Standard Error 0.005	-0.00 10^3 c/µL Standard Error 0.006
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 115 (n=98, 92, 95, 57)	0.01 10^3 c/µL Standard Error 0.006	0.01 10^3 c/µL Standard Error 0.004	0.01 10^3 c/µL Standard Error 0.004	0.00 10^3 c/µL Standard Error 0.007
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 128 (n=90, 87, 88, 50)	0.01 10^3 c/µL Standard Error 0.005	0.01 10^3 c/µL Standard Error 0.005	0.02 10^3 c/µL Standard Error 0.005	-0.00 10^3 c/µL Standard Error 0.008
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 141 (n=85, 78, 84, 47)	0.01 10^3 c/µL Standard Error 0.004	0.01 10^3 c/µL Standard Error 0.005	0.01 10^3 c/µL Standard Error 0.003	-0.01 10^3 c/µL Standard Error 0.008
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 154 (n=77, 71, 78, 45)	0.01 10^3 c/µL Standard Error 0.005	0.00 10^3 c/µL Standard Error 0.005	0.00 10^3 c/µL Standard Error 0.005	-0.01 10^3 c/µL Standard Error 0.007
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 167 (n=76, 67, 75, 42)	0.01 10^3 c/µL Standard Error 0.006	0.01 10^3 c/µL Standard Error 0.005	0.01 10^3 c/µL Standard Error 0.005	-0.00 10^3 c/µL Standard Error 0.008
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 180 (n=69, 60, 72, 41)	-0.00 10^3 c/µL Standard Error 0.006	-0.00 10^3 c/µL Standard Error 0.005	0.01 10^3 c/µL Standard Error 0.004	-0.01 10^3 c/µL Standard Error 0.006
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 193 (n=69, 60, 71, 40)	0.00 10^3 c/µL Standard Error 0.006	0.01 10^3 c/µL Standard Error 0.006	0.00 10^3 c/µL Standard Error 0.004	-0.01 10^3 c/µL Standard Error 0.008
Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period Change from BL at Week 206 (n=61, 48, 63, 31)	0.01 10^3 c/µL Standard Error 0.006	0.01 10^3 c/µL Standard Error 0.005	0.01 10^3 c/µL Standard Error 0.005	-0.01 10^3 c/µL Standard Error 0.008