Trial Outcomes & Findings for Saxagliptin Treatment in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise (NCT NCT00121641)

Last Updated: 2015-04-03

Results Overview

To compare the change from baseline in HbA1c achieved with each dose of saxagliptin versus placebo in treatment naive subjects with type 2 diabetes who have inadequate glycemic control defined as A1C ≥7.0% and ≤10.0%.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1035 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2015-04-03

Participant Flow

1035 subjects were enrolled; 422 entered the 2-week dietary/exercise placebo lead-in. 21 did not enter double-blind treatment period (19 discontinued, 2 randomized but did not receive study drug). 68 with screening hemoglobin A1c (A1C) \>10.0% and ≤12.0% entered directly in the open-label cohort; 66 received at least 1 dose of saxagliptin 10mg.

Participant milestones

Participant milestones
Measure	Saxagliptin 2.5 mg Tablets, Oral, 2.5 mg, Once daily (24 weeks short term \[ST\], 42 months long term \[LT\]); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)	Open-Label Treatment Cohort (Direct Enrollees) Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
24-week Short-term Treatment Period STARTED	102	106	98	95	66
24-week Short-term Treatment Period COMPLETED	73	68	69	55	25
24-week Short-term Treatment Period NOT COMPLETED	29	38	29	40	41
48-month Short Term + Long Term Period STARTED	102	106	98	95	66
48-month Short Term + Long Term Period COMPLETED	23	24	28	24	8
48-month Short Term + Long Term Period NOT COMPLETED	79	82	70	71	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Saxagliptin 2.5 mg Tablets, Oral, 2.5 mg, Once daily (24 weeks short term \[ST\], 42 months long term \[LT\]); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)	Open-Label Treatment Cohort (Direct Enrollees) Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
24-week Short-term Treatment Period Lack of Efficacy	15	21	14	25	30
24-week Short-term Treatment Period Subject Withdrew Consent	9	11	5	10	3
24-week Short-term Treatment Period Adverse Event	3	3	4	0	2
24-week Short-term Treatment Period Lost to Follow-up	0	2	3	4	4
24-week Short-term Treatment Period Poor / Non-compliance	0	0	3	1	1
24-week Short-term Treatment Period Subject No Longer Meets Study Criteria	1	1	0	0	1
24-week Short-term Treatment Period Other Reason	1	0	0	0	0
48-month Short Term + Long Term Period Lack of Efficacy	26	27	21	26	25
48-month Short Term + Long Term Period Subject Withdrew Consent	25	28	17	24	10
48-month Short Term + Long Term Period Adverse Event	9	10	10	5	5
48-month Short Term + Long Term Period Lost to Follow-up	9	7	12	11	12
48-month Short Term + Long Term Period Poor / Non-compliance	4	1	4	2	2
48-month Short Term + Long Term Period Subject No Longer Meets Study Criteria	1	3	2	1	2
48-month Short Term + Long Term Period Pregnancy	0	1	0	1	0
48-month Short Term + Long Term Period Administrative Reason by Sponsor	0	2	1	0	1
48-month Short Term + Long Term Period Death	0	0	0	1	0
48-month Short Term + Long Term Period Missing	0	0	1	0	0
48-month Short Term + Long Term Period Other Reason	5	3	2	0	1

Baseline Characteristics

Saxagliptin Treatment in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)	Total n=401 Participants Total of all reporting groups
Age, Continuous	53.27 years STANDARD_DEVIATION 10.06 • n=5 Participants	53.91 years STANDARD_DEVIATION 11.57 • n=7 Participants	52.73 years STANDARD_DEVIATION 11.27 • n=5 Participants	53.91 years STANDARD_DEVIATION 12.32 • n=4 Participants	53.46 years STANDARD_DEVIATION 11.29 • n=21 Participants
Age, Customized <65 years	91 participants n=5 Participants	86 participants n=7 Participants	84 participants n=5 Participants	77 participants n=4 Participants	338 participants n=21 Participants
Age, Customized >= 65 years	11 participants n=5 Participants	20 participants n=7 Participants	14 participants n=5 Participants	18 participants n=4 Participants	63 participants n=21 Participants
Age, Customized >=75 years	2 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants	6 participants n=21 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	52 Participants n=7 Participants	53 Participants n=5 Participants	48 Participants n=4 Participants	197 Participants n=21 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	54 Participants n=7 Participants	45 Participants n=5 Participants	47 Participants n=4 Participants	204 Participants n=21 Participants
Race/Ethnicity, Customized White	89 participants n=5 Participants	93 participants n=7 Participants	80 participants n=5 Participants	79 participants n=4 Participants	341 participants n=21 Participants
Race/Ethnicity, Customized Black/African American	5 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	22 participants n=21 Participants
Race/Ethnicity, Customized Asian	5 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	3 participants n=4 Participants	18 participants n=21 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	7 participants n=4 Participants	20 participants n=21 Participants
Race/Ethnicity, Customized Not Reported	41 Partcipants n=5 Participants	43 Partcipants n=7 Participants	42 Partcipants n=5 Participants	42 Partcipants n=4 Participants	168 Partcipants n=21 Participants
Race/Ethnicity, Customized Hispanic / Latino	16 Partcipants n=5 Participants	14 Partcipants n=7 Participants	14 Partcipants n=5 Participants	15 Partcipants n=4 Participants	59 Partcipants n=21 Participants
Race/Ethnicity, Customized Not Hispanic / Latino	45 Partcipants n=5 Participants	49 Partcipants n=7 Participants	42 Partcipants n=5 Participants	38 Partcipants n=4 Participants	174 Partcipants n=21 Participants
Age Categorization, Female Only =< 50 years	17 Participants n=5 Participants	24 Participants n=7 Participants	22 Participants n=5 Participants	19 Participants n=4 Participants	82 Participants n=21 Participants
Age Categorization, Female Only > 50 years	27 Participants n=5 Participants	28 Participants n=7 Participants	31 Participants n=5 Participants	29 Participants n=4 Participants	115 Participants n=21 Participants
Weight	92.10 kg STANDARD_DEVIATION 18.39 • n=5 Participants	91.09 kg STANDARD_DEVIATION 18.53 • n=7 Participants	89.30 kg STANDARD_DEVIATION 17.67 • n=5 Participants	86.56 kg STANDARD_DEVIATION 16.90 • n=4 Participants	89.84 kg STANDARD_DEVIATION 17.96 • n=21 Participants
Body Mass Index	31.90 kg/m^2 STANDARD_DEVIATION 4.82 • n=5 Participants	32.30 kg/m^2 STANDARD_DEVIATION 4.53 • n=7 Participants	31.71 kg/m^2 STANDARD_DEVIATION 4.71 • n=5 Participants	30.93 kg/m^2 STANDARD_DEVIATION 4.26 • n=4 Participants	31.73 kg/m^2 STANDARD_DEVIATION 4.60 • n=21 Participants
Body Mass Index Categorization < 30	36 Participants n=5 Participants	40 Participants n=7 Participants	35 Participants n=5 Participants	42 Participants n=4 Participants	153 Participants n=21 Participants
Body Mass Index Categorization >= 30	66 Participants n=5 Participants	66 Participants n=7 Participants	63 Participants n=5 Participants	53 Participants n=4 Participants	248 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).

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Hemoglobin A1c (A1C) Changes From Baseline at Week 24 Baseline Mean	7.91 Percentage of glycosylated hemoglobins Standard Error 0.09	7.98 Percentage of glycosylated hemoglobins Standard Error 0.11	7.85 Percentage of glycosylated hemoglobins Standard Error 0.09	7.88 Percentage of glycosylated hemoglobins Standard Error 0.10
Hemoglobin A1c (A1C) Changes From Baseline at Week 24 Adjusted Mean Change from Baseline	-0.43 Percentage of glycosylated hemoglobins Standard Error 0.10	-0.46 Percentage of glycosylated hemoglobins Standard Error 0.10	-0.54 Percentage of glycosylated hemoglobins Standard Error 0.10	0.19 Percentage of glycosylated hemoglobins Standard Error 0.10

PRIMARY outcome

Timeframe: Baseline, Week 24

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=64 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
A1C Changes From Baseline at Week 24 - Open Label Cohort Baseline Mean	10.70 Percentage of glycosylated hemoglobins Standard Error 0.10	—	—	—
A1C Changes From Baseline at Week 24 - Open Label Cohort Mean Change from Baseline	-1.87 Percentage of glycosylated hemoglobins Standard Error 0.18	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Randomized participants with measure at given time points, Last Observation Carried Forward (LOCF).

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=101 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=105 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=97 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=92 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) Baseline	177.72 mg/dL Standard Error 4.12	171.31 mg/dL Standard Error 4.09	176.51 mg/dL Standard Error 4.43	171.85 mg/dL Standard Error 4.80
Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) Adjusted Change from Baseline	-14.53 mg/dL Standard Error 3.82	-8.67 mg/dL Standard Error 3.74	-16.75 mg/dL Standard Error 3.89	6.06 mg/dL Standard Error 4.00

SECONDARY outcome

Timeframe: Week 24

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=100 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=103 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=95 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=92 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24	35.0 percentage of participants	37.9 percentage of participants	41.1 percentage of participants	23.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Randomized participants with measure at given time points, Last Observation Carried Forward (LOCF).

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=74 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=79 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=73 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=66 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) Baseline	45030 mg*min/dL Standard Error 1368.1	45691 mg*min/dL Standard Error 1209.8	44614 mg*min/dL Standard Error 1394.0	46030 mg*min/dL Standard Error 1397.8
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) Adjusted Change from Baseline	-6868 mg*min/dL Standard Error 1167.7	-6896 mg*min/dL Standard Error 1130.2	-8084 mg*min/dL Standard Error 1176.2	-646.6 mg*min/dL Standard Error 1236.9

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Open Label Subjects with Measurement at Timepoint; Last Observation Carried Forward (LOCF)

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=64 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) - Open Label Cohort Baseline	241.08 mg/dL Standard Error 6.19	—	—	—
Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) - Open Label Cohort Change from Baseline	-33.42 mg/dL Standard Error 5.37	—	—	—

SECONDARY outcome

Timeframe: Week 24

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=64 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24 - Open Label Cohort	14.1 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Open Label participants with measure at given time points, Last Observation Carried Forward (LOCF).

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=64 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) - Open Label Cohort Baseline	60687 mg*min/dL Standard Error 2312.4	—	—	—
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) - Open Label Cohort Change from Baseline	-11078 mg*min/dL Standard Error 2132.8	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

This cohort represents a different population (screening A1C \> 10.0% and ≤ 12.0%) than the double-blind cohort, and was presented separately in the study report.

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline Demographic Characteristic (Age, Continuous) - Summary for ST + LT Treatment Period - Open-Label Cohort	49.09 years Standard Deviation 8.63	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

This cohort represents a different population (screening A1C \> 10.0% and ≤ 12.0%) than the double-blind cohort, and was presented separately in the study report.

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Age >50 years, females only	15 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Age <65 years	64 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Age >=65 years	2 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Age >=75 years	0 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Gender, Male	32 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Gender, Female	34 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Age =<50 years, females only	19 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Race, White	61 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Race, Black/African American	3 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Race, Asian	1 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Race, Other	1 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Ethnicity, Hispanic/Latino	13 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Ethnicity, Not Hispanic/Latino	37 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Ethnicity, Not Reported	16 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Body Mass Index <30%	22 participants	—	—	—
Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort Body Mass Index >=30%	44 participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

This cohort represents a different population (screening A1C \> 10.0% and ≤ 12.0%) than the double-blind cohort, and was presented separately in the study report.

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline Demographic Characteristic (Weight) - Summary for ST + LT Treatment Period - Open-Label Cohort	91.41 kg Standard Deviation 20.65	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

This cohort represents a different population (screening A1C \> 10.0% and ≤ 12.0%) than the double-blind cohort, and was presented separately in the study report.

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline Demographic Characteristic (Body Mass Index) - Summary for ST + LT Treatment Period - Open-Label Cohort	31.73 kg/m^2 Standard Deviation 4.73	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm.

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 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 AE	89 participants	94 participants	87 participants	77 participants
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 Related AE	25 participants	23 participants	25 participants	25 participants
Overall Summary of Adverse Events During ST+LT Treatment Period Deaths	0 participants	0 participants	0 participants	1 participants
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 SAE	11 participants	18 participants	9 participants	11 participants
Overall Summary of Adverse Events During ST+LT Treatment Period At Least 1 Related SAE	0 participants	1 participants	0 participants	0 participants
Overall Summary of Adverse Events During ST+LT Treatment Period Discontinuations Due to SAEs	6 participants	2 participants	3 participants	1 participants
Overall Summary of Adverse Events During ST+LT Treatment Period Discontinuations Due to AEs	9 participants	10 participants	10 participants	5 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 was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm.

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 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Marked Laboratory Abnormalities - During ST + LT Treatment Period Hemoglobin < 8 g/dL (n=101, 105, 97, 93)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Hematocrit < 0.75 x pre-Rx (n=101, 105, 97, 93)	0 participants	0 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Platelets < 50 x 10^9 c/L (n=100, 104, 94, 93)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Platelets > 1.5 x ULN (n=100,104, 94, 93)	1 participants	0 participants	0 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Leukocytes < 2 x 1000 c/µL (n=101, 105, 97, 93)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Neutrophils+Bands <1x1000 c/µL(n=101, 105, 97, 93)	0 participants	0 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Eosinophils >0.9x1000 c/µL (n=101, 105, 97, 93)	1 participants	5 participants	3 participants	4 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Lymphocytes <=0.75x1000 c/µL (n=101, 105, 97, 93)	4 participants	2 participants	2 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALP >3 x pre-Rx and >ULN (n=101,105, 97, 94)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALP >1.5 x ULN (n=101, 105, 97, 94)	2 participants	1 participants	1 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >3 x ULN (n=101, 105, 97, 94)	3 participants	2 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >5 x ULN (n=101, 105, 97, 94)	2 participants	1 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >10 x ULN (n=101, 105, 97, 94)	1 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period AST >20 x ULN (n=101, 105, 97, 94)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >3 x ULN (n=101, 105, 97, 94)	3 participants	2 participants	0 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >5 x ULN (n=101, 105, 97, 94)	1 participants	1 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >10 x ULN (n=101, 105, 97, 94)	1 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period ALT >20 x ULN (n=101, 105, 97, 94)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Bilirubin Total >2mg/dL (n=101, 105, 97, 94)	1 participants	0 participants	3 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Bilirubin Total >1.5xULN (n=101, 105, 97, 94)	1 participants	0 participants	3 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Bilirubin Total >2xULN (n=101, 105, 97, 94)	1 participants	0 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period BUN >2 x pre-Rx and >ULN (n=101, 105, 97, 94)	1 participants	3 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Creatinine >2.5 mg/dL (n=101, 105, 97, 94)	1 participants	0 participants	0 participants	0 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=101, 104, 96,94)	1 participants	0 participants	1 participants	2 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose,Plasma Fasting>500mg/dL(n=101, 104, 96,94)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose, Plasma Unspec.<50mg/dL(n=102, 105, 98,95)	7 participants	4 participants	4 participants	3 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Glucose,Plasma Unspec.>500mg/dL(n=102, 105, 98,95)	0 participants	1 participants	0 participants	2 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Sodium,Serum Low (see above) (n=101, 105, 97, 94)	0 participants	0 participants	0 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Sodium,Serum High(see above) (n=101, 105, 97, 94)	1 participants	0 participants	1 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Potassium,Serum Low(see above)(n=101, 105, 97, 94)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Potassium, Serum High(see above)(n=101,105,97,94)	3 participants	3 participants	1 participants	3 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Chloride < 90 mEq/L (n=101, 105, 97, 94)	0 participants	0 participants	0 participants	1 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Chloride > 120 mEq/L (n=101, 105, 97, 94)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Albumin < 0.9 LLN (n=101, 105, 97, 94)	0 participants	0 participants	0 participants	0 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Creatine Kinase > 5 x ULN (n=101, 105, 97, 94)	2 participants	4 participants	1 participants	4 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 Protein Urine, >=2-4 (n=99, 103, 94, 92)	8 participants	9 participants	4 participants	3 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Blood Urine, >=2-4 (n=99, 103, 94, 92)	5 participants	11 participants	8 participants	16 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period Red Blood Cells Urine >=2-4 (n=95, 97, 89, 88)	6 participants	8 participants	8 participants	14 participants
Marked Laboratory Abnormalities - During ST + LT Treatment Period White Blood Cells Urine >=2-4 (n=95, 97, 89, 88)	13 participants	19 participants	15 participants	12 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 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Baseline (BL) (Week 0) (n=102, 106, 98, 94)	14.49 g/dL Standard Error 0.133	14.45 g/dL Standard Error 0.125	14.47 g/dL Standard Error 0.137	14.50 g/dL Standard Error 0.131
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 2 (n=95,100, 93, 87)	-0.21 g/dL Standard Error 0.069	-0.13 g/dL Standard Error 0.065	-0.22 g/dL Standard Error 0.075	-0.09 g/dL Standard Error 0.078
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 4 (n=92, 99, 91, 91)	-0.16 g/dL Standard Error 0.071	-0.15 g/dL Standard Error 0.082	-0.09 g/dL Standard Error 0.069	0.10 g/dL Standard Error 0.063
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 6 (n=91, 96, 87, 82)	-0.12 g/dL Standard Error 0.069	-0.00 g/dL Standard Error 0.074	-0.07 g/dL Standard Error 0.073	0.04 g/dL Standard Error 0.069
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 8 (n=92, 90, 91, 79)	-0.00 g/dL Standard Error 0.068	0.04 g/dL Standard Error 0.080	-0.02 g/dL Standard Error 0.071	0.09 g/dL Standard Error 0.074
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 10 (n=70, 76, 69, 63)	0.01 g/dL Standard Error 0.082	-0.20 g/dL Standard Error 0.096	-0.13 g/dL Standard Error 0.086	0.04 g/dL Standard Error 0.097
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 12 (n=85, 88, 87, 82)	-0.04 g/dL Standard Error 0.074	-0.07 g/dL Standard Error 0.079	-0.07 g/dL Standard Error 0.083	0.16 g/dL Standard Error 0.075
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 14 (n=76, 80, 81, 75)	-0.09 g/dL Standard Error 0.090	-0.05 g/dL Standard Error 0.078	-0.12 g/dL Standard Error 0.085	-0.03 g/dL Standard Error 0.083
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 16 (n=90, 91, 83, 71)	-0.10 g/dL Standard Error 0.087	0.01 g/dL Standard Error 0.078	0.00 g/dL Standard Error 0.087	0.04 g/dL Standard Error 0.084
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 18 (n=78, 75, 82, 71)	-0.26 g/dL Standard Error 0.083	-0.10 g/dL Standard Error 0.079	-0.07 g/dL Standard Error 0.092	-0.03 g/dL Standard Error 0.099
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 20 (n=83, 80, 78, 72)	-0.16 g/dL Standard Error 0.079	-0.14 g/dL Standard Error 0.093	-0.25 g/dL Standard Error 0.081	-0.19 g/dL Standard Error 0.086
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 22 (n=78, 74, 76, 65)	-0.35 g/dL Standard Error 0.075	-0.23 g/dL Standard Error 0.092	-0.36 g/dL Standard Error 0.087	-0.18 g/dL Standard Error 0.102
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 24 (n=83, 82, 78, 74)	-0.37 g/dL Standard Error 0.079	-0.25 g/dL Standard Error 0.080	-0.32 g/dL Standard Error 0.078	-0.14 g/dL Standard Error 0.100
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 30 (n=77, 78, 79, 67)	-0.25 g/dL Standard Error 0.081	-0.29 g/dL Standard Error 0.097	-0.19 g/dL Standard Error 0.086	-0.18 g/dL Standard Error 0.101
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 37 (n=75, 73, 70, 62)	-0.31 g/dL Standard Error 0.094	-0.22 g/dL Standard Error 0.087	-0.06 g/dL Standard Error 0.090	-0.33 g/dL Standard Error 0.093
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 50 (n=67, 71, 71, 61)	-0.17 g/dL Standard Error 0.082	0.06 g/dL Standard Error 0.103	-0.02 g/dL Standard Error 0.107	-0.01 g/dL Standard Error 0.100
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 63 (n=61, 66, 67, 55)	-0.18 g/dL Standard Error 0.112	-0.11 g/dL Standard Error 0.096	0.07 g/dL Standard Error 0.102	0.08 g/dL Standard Error 0.139
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 76 (n=51, 59, 63, 49)	-0.27 g/dL Standard Error 0.125	-0.19 g/dL Standard Error 0.119	-0.07 g/dL Standard Error 0.102	-0.10 g/dL Standard Error 0.117
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 89 (n=49, 58, 56, 42)	-0.18 g/dL Standard Error 0.109	-0.09 g/dL Standard Error 0.097	-0.04 g/dL Standard Error 0.103	-0.10 g/dL Standard Error 0.109
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 102 (n=40, 49, 51, 40)	-0.32 g/dL Standard Error 0.132	-0.00 g/dL Standard Error 0.129	-0.07 g/dL Standard Error 0.121	-0.29 g/dL Standard Error 0.131
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 115 (n=34, 43, 43, 35)	-0.41 g/dL Standard Error 0.132	-0.07 g/dL Standard Error 0.137	-0.18 g/dL Standard Error 0.147	-0.19 g/dL Standard Error 0.116
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 128 (n=30, 40, 40, 30)	-0.38 g/dL Standard Error 0.125	-0.17 g/dL Standard Error 0.128	-0.25 g/dL Standard Error 0.132	-0.33 g/dL Standard Error 0.124
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 141 (n=28, 39, 34, 28)	-0.40 g/dL Standard Error 0.125	-0.35 g/dL Standard Error 0.156	-0.15 g/dL Standard Error 0.169	-0.36 g/dL Standard Error 0.104
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 154 (n=26, 34, 31, 24)	-0.45 g/dL Standard Error 0.160	-0.37 g/dL Standard Error 0.186	-0.24 g/dL Standard Error 0.166	-0.25 g/dL Standard Error 0.130
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 167 (n=24, 33, 30, 26)	-0.51 g/dL Standard Error 0.178	-0.05 g/dL Standard Error 0.161	-0.03 g/dL Standard Error 0.170	-0.24 g/dL Standard Error 0.148
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 180 (n=21, 28, 28, 26)	-0.38 g/dL Standard Error 0.178	-0.08 g/dL Standard Error 0.176	-0.08 g/dL Standard Error 0.167	-0.61 g/dL Standard Error 0.169
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 193 (n=19, 26, 26, 23)	-0.45 g/dL Standard Error 0.212	-0.03 g/dL Standard Error 0.190	-0.16 g/dL Standard Error 0.178	-0.39 g/dL Standard Error 0.175
Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period Change from BL at Week 206 (n=17, 22, 24, 21)	-0.51 g/dL Standard Error 0.221	-0.07 g/dL Standard Error 0.195	0.10 g/dL Standard Error 0.124	-0.32 g/dL Standard Error 0.174

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
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 2 (n=96, 100, 94, 89)	-0.1 beats per minute Standard Error 0.9	-0.5 beats per minute Standard Error 0.8	0.2 beats per minute Standard Error 0.8	0.3 beats per minute Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 4 (n=96, 100, 92, 91)	0.2 beats per minute Standard Error 0.9	-1.1 beats per minute Standard Error 0.8	0.7 beats per minute Standard Error 0.7	-0.1 beats per minute Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 6 (n=91, 98, 88, 84)	-1.5 beats per minute Standard Error 0.9	-0.6 beats per minute Standard Error 0.8	-0.6 beats per minute Standard Error 0.8	1.4 beats per minute Standard Error 1.0
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 8 (n=94, 91, 91, 80)	-0.5 beats per minute Standard Error 0.9	-0.9 beats per minute Standard Error 0.8	0.2 beats per minute Standard Error 0.8	-0.2 beats per minute Standard Error 0.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 10 (n=51, 66, 51, 49)	-0.2 beats per minute Standard Error 1.2	-1.5 beats per minute Standard Error 0.9	-1.0 beats per minute Standard Error 1.2	0.1 beats per minute Standard Error 1.3
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 12 (n=82, 83, 87, 79)	0.3 beats per minute Standard Error 1.0	-1.2 beats per minute Standard Error 0.8	0.5 beats per minute Standard Error 0.9	0.8 beats per minute Standard Error 1.1
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 14 (n=65, 72, 65, 62)	0.1 beats per minute Standard Error 1.1	-0.5 beats per minute Standard Error 0.9	0.6 beats per minute Standard Error 1.1	1.9 beats per minute Standard Error 1.1
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 16 (n=87, 87, 81, 72)	-0.8 beats per minute Standard Error 0.9	-1.5 beats per minute Standard Error 0.9	-0.1 beats per minute Standard Error 0.9	-0.1 beats per minute Standard Error 1.0
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 18 (n=73, 69, 76, 66)	-0.0 beats per minute Standard Error 1.1	-0.8 beats per minute Standard Error 1.1	1.5 beats per minute Standard Error 1.0	2.6 beats per minute Standard Error 1.0
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 20 (n=84, 80, 76, 73)	1.3 beats per minute Standard Error 0.9	-1.5 beats per minute Standard Error 0.9	1.3 beats per minute Standard Error 0.9	0.8 beats per minute Standard Error 1.1
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 22 (n=78, 73, 76, 64)	0.1 beats per minute Standard Error 1.0	-0.3 beats per minute Standard Error 0.9	0.9 beats per minute Standard Error 0.9	1.5 beats per minute Standard Error 1.0
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 24 (n=84, 83, 77, 75)	-0.3 beats per minute Standard Error 1.1	0.1 beats per minute Standard Error 1.1	-0.7 beats per minute Standard Error 0.9	-0.4 beats per minute Standard Error 1.1
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 30 (n=79, 78, 79, 66)	-0.1 beats per minute Standard Error 1.0	-1.2 beats per minute Standard Error 1.1	-0.7 beats per minute Standard Error 0.8	-1.2 beats per minute Standard Error 1.3
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 37 (n=77, 74, 71, 66)	-0.4 beats per minute Standard Error 1.0	-1.4 beats per minute Standard Error 0.9	0.5 beats per minute Standard Error 1.0	-0.9 beats per minute Standard Error 1.2
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 50 (n=70, 73, 73, 62)	-0.1 beats per minute Standard Error 0.9	-0.7 beats per minute Standard Error 1.1	-0.2 beats per minute Standard Error 1.0	-0.2 beats per minute Standard Error 1.2
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 63 (n=62, 66, 69, 56)	-0.4 beats per minute Standard Error 1.1	-2.5 beats per minute Standard Error 1.0	0.9 beats per minute Standard Error 1.1	0.6 beats per minute Standard Error 1.4
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 76 (n=53, 59, 64, 50)	-0.3 beats per minute Standard Error 1.4	-3.3 beats per minute Standard Error 1.1	0.4 beats per minute Standard Error 1.1	0.2 beats per minute Standard Error 1.6
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 89 (n=49, 58, 56, 44)	-0.5 beats per minute Standard Error 1.4	-1.5 beats per minute Standard Error 1.2	-0.9 beats per minute Standard Error 1.1	-0.3 beats per minute Standard Error 1.3
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 102 (n=42, 51, 51, 42)	-2.8 beats per minute Standard Error 1.4	-1.5 beats per minute Standard Error 1.4	-0.1 beats per minute Standard Error 1.4	-0.0 beats per minute Standard Error 1.6
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 115 (n=34, 43, 43, 37)	-3.2 beats per minute Standard Error 1.7	-2.3 beats per minute Standard Error 1.3	1.0 beats per minute Standard Error 1.6	0.8 beats per minute Standard Error 1.9
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 128 (n=31, 40, 41, 31)	-2.1 beats per minute Standard Error 1.8	-4.5 beats per minute Standard Error 1.6	-0.7 beats per minute Standard Error 1.4	1.7 beats per minute Standard Error 1.8
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 141 (n=29, 40, 35, 29)	-2.8 beats per minute Standard Error 1.4	-3.5 beats per minute Standard Error 1.5	-0.6 beats per minute Standard Error 1.6	0.9 beats per minute Standard Error 1.7
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 154 (n=27, 36, 33, 27)	-2.0 beats per minute Standard Error 2.1	-2.6 beats per minute Standard Error 1.6	-1.3 beats per minute Standard Error 1.8	-0.6 beats per minute Standard Error 2.0
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 167 (n=24, 33, 30, 27)	-5.1 beats per minute Standard Error 1.9	-0.8 beats per minute Standard Error 1.4	-2.1 beats per minute Standard Error 2.4	0.5 beats per minute Standard Error 1.6
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 180 (n=21, 28, 28, 27)	-3.1 beats per minute Standard Error 2.1	-5.3 beats per minute Standard Error 1.8	-2.0 beats per minute Standard Error 2.0	-1.2 beats per minute Standard Error 1.4
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 193 (n=19, 26, 27, 24)	-4.6 beats per minute Standard Error 2.4	-4.2 beats per minute Standard Error 1.8	-2.4 beats per minute Standard Error 2.0	1.1 beats per minute Standard Error 2.1
Changes From Baseline in Heart Rate During the ST + LT Period Change from BL at Week 206 (n=17, 24, 24, 23)	-5.3 beats per minute Standard Error 2.6	-2.6 beats per minute Standard Error 1.9	0.0 beats per minute Standard Error 2.7	-0.8 beats per minute Standard Error 2.1

OTHER_PRE_SPECIFIED outcome

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

Population: Treated participants; BL n=number of participants at baseline

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 206 (BL n=4, 13, 8, 11)	2 participants	10 participants	4 participants	7 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 12 (BL n=65, 66, 67, 47)	57 participants	56 participants	59 participants	43 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 12 (BL n=65, 66, 67, 47)	8 participants	10 participants	8 participants	4 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 12 (BL n=27, 32, 26, 43)	6 participants	6 participants	9 participants	15 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 12(BL n=27, 32, 26, 43)	21 participants	26 participants	17 participants	28 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 24 (BL n=53, 52, 47, 33)	43 participants	44 participants	43 participants	31 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 24 (BL n=53, 52, 47, 33)	10 participants	8 participants	4 participants	2 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 24 (BL n=19, 24, 21, 25)	5 participants	8 participants	9 participants	8 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Abnormal Week 24(BL n=19, 24, 21, 25)	14 participants	16 participants	12 participants	17 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 76 (BL n=48, 49, 48, 36)	37 participants	44 participants	40 participants	30 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 76 (BL n=48, 49, 48, 36)	11 participants	5 participants	8 participants	6 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 76 (BL n=19, 23, 21, 27)	8 participants	8 participants	6 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=19, 23, 21, 27)	11 participants	15 participants	15 participants	14 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 102 (BL n=32, 32, 36, 22)	25 participants	26 participants	31 participants	18 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 102 (BL n=32, 32, 36, 22)	7 participants	6 participants	5 participants	4 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 102 (BL n=12, 18, 17, 20)	4 participants	5 participants	12 participants	11 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL,Abnormal Week 102(BL n=12, 18, 17, 20)	8 participants	13 participants	5 participants	9 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 154 (BL n=20, 21, 26, 15)	16 participants	17 participants	23 participants	14 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 154 (BL n=20, 21, 26, 15)	4 participants	4 participants	3 participants	1 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 154 (BL n=7, 16, 11, 13)	4 participants	4 participants	5 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=7, 16, 11, 13)	3 participants	12 participants	6 participants	6 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Normal Week 206 (BL n=15, 13, 20, 14)	15 participants	12 participants	18 participants	11 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Normal BL, Abnormal Week 206 (BL n=15, 13, 20, 14)	0 participants	1 participants	2 participants	3 participants
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period Abnormal BL, Normal Week 206 (BL n=4, 13, 8, 11)	2 participants	3 participants	4 participants	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks.

Population: All treated participants

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort At Least 1 AE	49 participants	—	—	—
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort At Least 1 Related AE	9 participants	—	—	—
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort Deaths	0 participants	—	—	—
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort At Least 1 SAE	6 participants	—	—	—
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort At Least 1 Related SAE	0 participants	—	—	—
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort Discontinuations Due to SAEs	2 participants	—	—	—
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort Discontinuations Due to AEs	5 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 was 34 weeks.

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Hemoglobin < 8 g/dL (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Hematocrit < 0.75 x pre-Rx (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Platelets < 50 x 10^9 c/L (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Platelets > 1.5 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Leukocytes < 2 x 1000 c/µL (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Neutrophils+Bands <1x1000 c/uL (n=64)	1 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Eosinophils >0.9x1000 c/µL (n=64)	2 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Lymphocytes <=0.75x1000 c/uL (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort ALP >3 x pre-Rx and >ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort ALP >1.5 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort AST >3 x ULN (n=64)	1 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort AST >5 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort AST >10 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort AST >20 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort ALT >3 x ULN (n=64)	1 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort ALT >5 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort ALT >10 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort ALT >20 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Bilirubin Total >2mg/dL (n=64)	1 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Bilirubin Total >1.5xULN (n=64)	1 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Bilirubin Total >2xULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort BUN >2 x pre-Rx and >ULN (n=64)	2 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Creatinine >2.5 mg/dL (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose, Serum Fasting < 50 mg/dL (n=1)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose, Serum Fasting > 500 mg/dL (n=1)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose, Serum Unspec. < 50 mg/dL (n=1)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose, Serum Unspec. > 500 mg/dL (n=1)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose, Plasma Fasting <50 mg/dL (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose,Plasma Fasting >500 mg/dL (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose, Plasma Unspec. <50 mg/dL (n=65)	2 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Glucose,Plasma Unspec. >500 mg/dL (n=65)	1 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Sodium,Serum Low (see above) (n=65)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Sodium,Serum High (see above) (n=65)	2 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Potassium,Serum Low (see above) (n=65)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Potassium, Serum High (see above) (n=65)	2 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Chloride < 90 mEq/L (n=65)	1 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Chloride > 120 mEq/L (n=65)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Albumin < 0.9 LLN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Creatine Kinase > 5 x ULN (n=64)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Uric Acid > 1.5 x ULN (n=0)	0 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Protein Urine, >=2-4 (n=64)	2 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Blood Urine, >=2-4 (n=64)	4 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort Red Blood Cells Urine >=2-4 (n=58)	7 participants	—	—	—
Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort White Blood Cells Urine >=2-4 (n=58)	6 participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Population: Treated participants

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
All Reported Hypoglycemic Adverse Events During ST + LT Treatment Period	9 participants	11 participants	10 participants	9 participants

OTHER_PRE_SPECIFIED outcome

Population: Treated participants

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Confirmed Hypoglycemia During ST + LT Treatment Period	1 participants	1 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks.

Population: Treated participants

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
All Reported Hypoglycemic Adverse Events During ST + LT Treatment Period - Open-Label Cohort	2 participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks.

Population: Treated participants

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Confirmed Hypoglycemia During ST + LT Treatment Period - Open-Label Cohort	0 participants	—	—	—

OTHER_PRE_SPECIFIED outcome

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

Population: Treated participants; BL n=number of participants at baseline

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Normal Week 12 (BL n=23)	19 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Abnormal Week 12 (BL n=23)	4 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Normal Week 12 (BL n=18)	5 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Abnormal Week 12 (BL n=18)	13 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Normal Week 24 (BL n=10)	8 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Abnormal Week 24 (BL n=10)	2 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Normal Week 24 (BL n=6)	2 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Abnormal Week 24(BL n=6)	4 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Normal Week 76 (BL n=17)	13 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Abnormal Week 76 (BL n=17)	4 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Normal Week 76 (BL n=13)	4 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Abnormal Week 76 (BL n=13)	9 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Normal Week 102 (BL n=8)	6 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Abnormal Week 102 (BL n=8)	2 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Normal Week 102 (BL n=4)	1 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Abnormal Week 102 (BL n=4)	3 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Normal Week 154 (BL n=4)	3 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Abnormal Week 154 (BL n=4)	1 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Normal Week 154 (BL n=2)	0 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Abnormal Week 154 (BL n=2)	2 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Normal Week 206 (BL n=3)	2 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Normal BL, Abnormal Week 206 (BL n=3)	1 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Normal Week 206 (BL n=1)	0 participants	—	—	—
Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort Abnormal BL, Abnormal Week 206 (BL n=1)	1 participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 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

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 2 (n=62)	-4.4 mmHg Standard Error 1.3	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 4 (n=59)	-3.8 mmHg Standard Error 1.4	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 6 (n=60)	-2.7 mmHg Standard Error 1.5	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 8 (n=49)	-5.1 mmHg Standard Error 1.6	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 10 (n=24)	-4.2 mmHg Standard Error 2.8	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 12 (n=47)	-4.9 mmHg Standard Error 1.8	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 14 (n=35)	-5.1 mmHg Standard Error 2.0	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 16 (n=46)	-1.9 mmHg Standard Error 2.2	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 18 (n=42)	-5.8 mmHg Standard Error 2.0	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 20 (n=45)	-3.6 mmHg Standard Error 2.0	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 22 (n=44)	-4.0 mmHg Standard Error 2.1	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 24 (n=44)	-4.3 mmHg Standard Error 2.1	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 30 (n=40)	-4.8 mmHg Standard Error 1.8	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 37 (n=35)	-4.7 mmHg Standard Error 1.8	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 50 (n=36)	-1.6 mmHg Standard Error 2.1	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 63 (n=26)	-0.7 mmHg Standard Error 2.7	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 76 (n=24)	-1.9 mmHg Standard Error 2.1	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 89 (n=23)	-4.0 mmHg Standard Error 2.6	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 102 (n=15)	0.9 mmHg Standard Error 2.4	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 115 (n=13)	-6.6 mmHg Standard Error 3.6	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 128 (n=11)	-5.6 mmHg Standard Error 4.3	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 141 (n=10)	-7.2 mmHg Standard Error 4.4	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 154 (n=10)	5.7 mmHg Standard Error 4.7	—	—	—
Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 167 (n=10)	-2.2 mmHg Standard Error 4.4	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 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

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 2 (n=62)	-3.7 mmHg Standard Error 0.9	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 4 (n=59)	-1.7 mmHg Standard Error 1.0	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 6 (n=60)	-2.8 mmHg Standard Error 1.0	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 8 (n=49)	-2.0 mmHg Standard Error 1.1	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 10 (n=24)	-1.0 mmHg Standard Error 2.0	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 12 (n=47)	-3.7 mmHg Standard Error 1.4	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 14 (n=35)	-4.5 mmHg Standard Error 1.7	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 16 (n=46)	-2.8 mmHg Standard Error 1.2	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 18 (n=42)	-3.3 mmHg Standard Error 1.1	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 20 (n=45)	-2.1 mmHg Standard Error 1.2	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 22 (n=44)	-2.8 mmHg Standard Error 1.5	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 24 (n=44)	-3.4 mmHg Standard Error 1.3	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 30 (n=40)	-3.8 mmHg Standard Error 1.5	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 37 (n=35)	-2.0 mmHg Standard Error 1.4	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 50 (n=36)	-1.3 mmHg Standard Error 1.4	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 63 (n=26)	-0.9 mmHg Standard Error 1.8	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 76 (n=24)	-1.0 mmHg Standard Error 2.0	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 89 (n=23)	-2.6 mmHg Standard Error 1.9	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 102 (n=15)	1.0 mmHg Standard Error 3.0	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 115 (n=13)	-4.1 mmHg Standard Error 2.5	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 128 (n=11)	-3.7 mmHg Standard Error 2.8	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 141 (n=10)	-6.0 mmHg Standard Error 2.6	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 154 (n=10)	-0.5 mmHg Standard Error 2.7	—	—	—
Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort Change from BL at Week 167 (n=10)	-2.5 mmHg Standard Error 2.9	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 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

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

Outcome measures

Outcome measures
Measure	Saxagliptin 2.5 mg n=66 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 2 (n=62)	-0.8 beats per minute Standard Error 1.0	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 4 (n=59)	-0.4 beats per minute Standard Error 1.1	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 6 (n=60)	-0.3 beats per minute Standard Error 1.0	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 8 (n=49)	-0.7 beats per minute Standard Error 1.5	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 10 (n=23)	-1.8 beats per minute Standard Error 2.1	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 12 (n=47)	-3.0 beats per minute Standard Error 1.1	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 14 (n=34)	-2.0 beats per minute Standard Error 1.4	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 16 (n=46)	-0.7 beats per minute Standard Error 1.1	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 18 (n=42)	-2.0 beats per minute Standard Error 1.3	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 20 (n=45)	1.6 beats per minute Standard Error 1.1	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 22 (n=43)	-0.4 beats per minute Standard Error 1.2	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 24 (n=44)	-0.4 beats per minute Standard Error 1.5	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 30 (n=40)	0.6 beats per minute Standard Error 1.3	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 37 (n=35)	-1.6 beats per minute Standard Error 1.6	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 50 (n=36)	-2.9 beats per minute Standard Error 1.3	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 63 (n=26)	-3.0 beats per minute Standard Error 1.6	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 76 (n=24)	-0.4 beats per minute Standard Error 2.5	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 89 (n=23)	-1.3 beats per minute Standard Error 1.8	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 102 (n=15)	-0.3 beats per minute Standard Error 1.6	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 115 (n=13)	1.7 beats per minute Standard Error 1.6	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 128 (n=11)	-1.6 beats per minute Standard Error 3.6	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 141 (n=10)	-3.4 beats per minute Standard Error 1.7	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 154 (n=10)	-1.5 beats per minute Standard Error 2.6	—	—	—
Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort Change from BL at Week 167 (n=10)	-1.9 beats per minute Standard Error 3.3	—	—	—

Adverse Events

Open-Label Treatment Cohort (Direct Enrollees)

Serious events: 6 serious events

Other events: 39 other events

Deaths: 0 deaths

Placebo

Serious events: 11 serious events

Other events: 63 other events

Deaths: 0 deaths

Saxagliptin 10 mg

Serious events: 9 serious events

Other events: 69 other events

Deaths: 0 deaths

Saxagliptin 2.5 mg

Serious events: 11 serious events

Other events: 72 other events

Deaths: 0 deaths

Saxagliptin 5 mg

Serious events: 18 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open-Label Treatment Cohort (Direct Enrollees) n=66 participants at risk Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 participants at risk Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)	Saxagliptin 10 mg n=98 participants at risk Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 2.5 mg n=102 participants at risk Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 participants at risk Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
Cardiac disorders TACHYCARDIA	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Cardiac disorders ANGINA UNSTABLE	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Cardiac disorders ATRIAL FIBRILLATION	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	1.9% 2/106
Cardiac disorders AORTIC VALVE STENOSIS	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Cardiac disorders CORONARY ARTERY DISEASE	0.00% 0/66	0.00% 0/95	0.00% 0/98	2.0% 2/102	0.94% 1/106
Cardiac disorders CARDIAC FAILURE CONGESTIVE	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Cardiac disorders SUPRAVENTRICULAR TACHYCARDIA	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Vascular disorders HYPOTENSION	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Vascular disorders HYPERTENSION	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Vascular disorders ORTHOSTATIC HYPOTENSION	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Endocrine disorders ADRENAL MASS	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Hepatobiliary disorders GALLBLADDER POLYP	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Nervous system disorders SYNCOPE	0.00% 0/66	1.1% 1/95	0.00% 0/98	2.0% 2/102	0.94% 1/106
Nervous system disorders SCIATICA	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Nervous system disorders VASCULAR HEADACHE	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Nervous system disorders IVTH NERVE PARALYSIS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	1.9% 2/106
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
Gastrointestinal disorders INTESTINAL MASS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Gastrointestinal disorders ABDOMINAL TENDERNESS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Infections and infestations GANGRENE	1.5% 1/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Infections and infestations PNEUMONIA	1.5% 1/66	1.1% 1/95	0.00% 0/98	2.0% 2/102	0.00% 0/106
Infections and infestations CELLULITIS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	1.9% 2/106
Infections and infestations HEPATITIS C	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Infections and infestations APPENDICITIS	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
Infections and infestations TUBERCULOSIS	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
Infections and infestations PYELONEPHRITIS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Infections and infestations GASTROENTERITIS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Infections and infestations HAEMATOMA INFECTION	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Renal and urinary disorders NEPHROLITHIASIS	1.5% 1/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Metabolism and nutrition disorders DEHYDRATION	1.5% 1/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Skin and subcutaneous tissue disorders RASH	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Reproductive system and breast disorders TESTICULAR PAIN	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Reproductive system and breast disorders BENIGN PROSTATIC HYPERPLASIA	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Injury, poisoning and procedural complications WOUND	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Injury, poisoning and procedural complications MULTIPLE FRACTURES	1.5% 1/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Pregnancy, puerperium and perinatal conditions ABORTION SPONTANEOUS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Musculoskeletal and connective tissue disorders BACK PAIN	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	1.9% 2/106
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
General disorders CHEST PAIN	0.00% 0/66	1.1% 1/95	1.0% 1/98	0.98% 1/102	0.00% 0/106
General disorders NON-CARDIAC CHEST PAIN	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON CANCER	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.94% 1/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BRAIN NEOPLASM	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	1.5% 1/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CERVIX CARCINOMA	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	0.00% 0/66	1.1% 1/95	0.00% 0/98	0.00% 0/102	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BASAL CELL CARCINOMA	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.98% 1/102	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RENAL CELL CARCINOMA	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM MALIGNANT	0.00% 0/66	0.00% 0/95	1.0% 1/98	0.00% 0/102	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.98% 1/102	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA OF SKIN	0.00% 0/66	0.00% 0/95	0.00% 0/98	0.00% 0/102	0.94% 1/106

Other adverse events

Other adverse events
Measure	Open-Label Treatment Cohort (Direct Enrollees) n=66 participants at risk Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 participants at risk Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)	Saxagliptin 10 mg n=98 participants at risk Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 2.5 mg n=102 participants at risk Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 participants at risk Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
Vascular disorders HYPERTENSION	3.0% 2/66	8.4% 8/95	3.1% 3/98	4.9% 5/102	6.6% 7/106
Psychiatric disorders INSOMNIA	1.5% 1/66	3.2% 3/95	3.1% 3/98	2.9% 3/102	5.7% 6/106
Psychiatric disorders DEPRESSION	4.5% 3/66	3.2% 3/95	6.1% 6/98	2.0% 2/102	6.6% 7/106
Nervous system disorders HEADACHE	12.1% 8/66	16.8% 16/95	16.3% 16/98	6.9% 7/102	12.3% 13/106
Nervous system disorders DIZZINESS	7.6% 5/66	8.4% 8/95	3.1% 3/98	3.9% 4/102	8.5% 9/106
Gastrointestinal disorders NAUSEA	9.1% 6/66	6.3% 6/95	4.1% 4/98	6.9% 7/102	5.7% 6/106
Gastrointestinal disorders VOMITING	4.5% 3/66	3.2% 3/95	1.0% 1/98	3.9% 4/102	6.6% 7/106
Gastrointestinal disorders DIARRHOEA	6.1% 4/66	8.4% 8/95	10.2% 10/98	13.7% 14/102	7.5% 8/106
Gastrointestinal disorders TOOTHACHE	0.00% 0/66	5.3% 5/95	2.0% 2/98	2.9% 3/102	2.8% 3/106
Gastrointestinal disorders CONSTIPATION	1.5% 1/66	5.3% 5/95	3.1% 3/98	2.9% 3/102	4.7% 5/106
Gastrointestinal disorders ABDOMINAL PAIN	3.0% 2/66	2.1% 2/95	1.0% 1/98	2.0% 2/102	6.6% 7/106
Infections and infestations INFLUENZA	6.1% 4/66	6.3% 6/95	15.3% 15/98	10.8% 11/102	8.5% 9/106
Infections and infestations SINUSITIS	3.0% 2/66	5.3% 5/95	10.2% 10/98	8.8% 9/102	7.5% 8/106
Infections and infestations BRONCHITIS	1.5% 1/66	6.3% 6/95	5.1% 5/98	2.0% 2/102	4.7% 5/106
Infections and infestations PHARYNGITIS	3.0% 2/66	6.3% 6/95	6.1% 6/98	3.9% 4/102	5.7% 6/106
Infections and infestations NASOPHARYNGITIS	12.1% 8/66	12.6% 12/95	14.3% 14/98	10.8% 11/102	12.3% 13/106
Infections and infestations URINARY TRACT INFECTION	9.1% 6/66	8.4% 8/95	10.2% 10/98	7.8% 8/102	13.2% 14/106
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	13.6% 9/66	15.8% 15/95	14.3% 14/98	11.8% 12/102	15.1% 16/106
Skin and subcutaneous tissue disorders RASH	6.1% 4/66	2.1% 2/95	5.1% 5/98	6.9% 7/102	7.5% 8/106
Injury, poisoning and procedural complications CONTUSION	1.5% 1/66	2.1% 2/95	2.0% 2/98	6.9% 7/102	1.9% 2/106
Musculoskeletal and connective tissue disorders BACK PAIN	7.6% 5/66	11.6% 11/95	5.1% 5/98	3.9% 4/102	11.3% 12/106
Musculoskeletal and connective tissue disorders ARTHRALGIA	6.1% 4/66	7.4% 7/95	16.3% 16/98	7.8% 8/102	5.7% 6/106
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	1.5% 1/66	6.3% 6/95	9.2% 9/98	8.8% 9/102	7.5% 8/106
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	7.6% 5/66	9.5% 9/95	6.1% 6/98	3.9% 4/102	4.7% 5/106
Respiratory, thoracic and mediastinal disorders COUGH	4.5% 3/66	5.3% 5/95	6.1% 6/98	4.9% 5/102	3.8% 4/106
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	6.1% 4/66	4.2% 4/95	3.1% 3/98	0.00% 0/102	2.8% 3/106

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 2.5 mg n=102 Participants Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 5 mg n=106 Participants Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Saxagliptin 10 mg n=98 Participants Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).	Placebo n=95 Participants Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Baseline (BL) (Week 0) (n=102, 106, 98, 94)	42.5 percentage red blood cells Standard Error 0.35	42.8 percentage red blood cells Standard Error 0.35	42.7 percentage red blood cells Standard Error 0.37	42.8 percentage red blood cells Standard Error 0.35
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 2 (n=95,100, 93, 87)	-0.4 percentage red blood cells Standard Error 0.22	-0.2 percentage red blood cells Standard Error 0.20	-0.7 percentage red blood cells Standard Error 0.21	-0.4 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 4 (n=92, 99, 91, 91)	-0.2 percentage red blood cells Standard Error 0.21	-0.2 percentage red blood cells Standard Error 0.24	-0.1 percentage red blood cells Standard Error 0.22	0.3 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 6 (n=91, 96, 87, 82)	0.1 percentage red blood cells Standard Error 0.19	0.3 percentage red blood cells Standard Error 0.24	0.0 percentage red blood cells Standard Error 0.24	0.3 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 8 (n=92, 90, 91, 79)	0.5 percentage red blood cells Standard Error 0.22	0.4 percentage red blood cells Standard Error 0.27	0.2 percentage red blood cells Standard Error 0.20	0.5 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 10 (n=70, 76, 69, 63)	0.6 percentage red blood cells Standard Error 0.25	-0.0 percentage red blood cells Standard Error 0.31	-0.2 percentage red blood cells Standard Error 0.24	0.5 percentage red blood cells Standard Error 0.32
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 12 (n=85, 88, 87, 82)	0.6 percentage red blood cells Standard Error 0.25	0.4 percentage red blood cells Standard Error 0.26	0.6 percentage red blood cells Standard Error 0.26	0.7 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 14 (n=76, 80, 81, 75)	0.6 percentage red blood cells Standard Error 0.27	0.6 percentage red blood cells Standard Error 0.27	0.2 percentage red blood cells Standard Error 0.27	0.2 percentage red blood cells Standard Error 0.26
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 16 (n=90. 91, 83, 71)	0.5 percentage red blood cells Standard Error 0.24	0.7 percentage red blood cells Standard Error 0.26	0.6 percentage red blood cells Standard Error 0.25	0.3 percentage red blood cells Standard Error 0.30
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 18 (n=78, 75, 82, 71)	0.2 percentage red blood cells Standard Error 0.27	0.4 percentage red blood cells Standard Error 0.29	0.3 percentage red blood cells Standard Error 0.24	0.4 percentage red blood cells Standard Error 0.30
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 20 (n=83, 80, 78, 72)	0.7 percentage red blood cells Standard Error 0.25	0.4 percentage red blood cells Standard Error 0.31	0.1 percentage red blood cells Standard Error 0.26	0.2 percentage red blood cells Standard Error 0.27
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 22 (n=78, 74, 76, 65)	0.3 percentage red blood cells Standard Error 0.27	0.2 percentage red blood cells Standard Error 0.32	-0.3 percentage red blood cells Standard Error 0.26	0.5 percentage red blood cells Standard Error 0.32
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 24 (n=83, 82, 78, 74)	0.0 percentage red blood cells Standard Error 0.24	0.2 percentage red blood cells Standard Error 0.28	-0.1 percentage red blood cells Standard Error 0.24	0.5 percentage red blood cells Standard Error 0.32
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 30 (n=77, 78, 79, 67)	0.5 percentage red blood cells Standard Error 0.30	-0.1 percentage red blood cells Standard Error 0.36	0.2 percentage red blood cells Standard Error 0.30	0.4 percentage red blood cells Standard Error 0.35
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 37 (n=75, 73, 70, 62)	0.0 percentage red blood cells Standard Error 0.30	-0.1 percentage red blood cells Standard Error 0.27	0.4 percentage red blood cells Standard Error 0.29	-0.4 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 50 (n=67, 71, 71, 61)	0.1 percentage red blood cells Standard Error 0.29	0.3 percentage red blood cells Standard Error 0.33	0.1 percentage red blood cells Standard Error 0.34	0.2 percentage red blood cells Standard Error 0.27
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 63 (n=61, 66, 67, 55)	0.3 percentage red blood cells Standard Error 0.34	0.1 percentage red blood cells Standard Error 0.31	0.6 percentage red blood cells Standard Error 0.34	0.7 percentage red blood cells Standard Error 0.43
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 76 (n=51, 59, 63, 49)	0.7 percentage red blood cells Standard Error 0.39	0.5 percentage red blood cells Standard Error 0.40	0.7 percentage red blood cells Standard Error 0.35	0.8 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 89 (n=49, 58, 56, 42)	0.9 percentage red blood cells Standard Error 0.37	0.9 percentage red blood cells Standard Error 0.34	1.2 percentage red blood cells Standard Error 0.35	0.4 percentage red blood cells Standard Error 0.36
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 102 (n=40, 49, 51, 40)	-0.2 percentage red blood cells Standard Error 0.37	0.5 percentage red blood cells Standard Error 0.40	-0.0 percentage red blood cells Standard Error 0.34	-0.7 percentage red blood cells Standard Error 0.36
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 115 (n=34, 43, 43, 35)	-0.0 percentage red blood cells Standard Error 0.42	0.6 percentage red blood cells Standard Error 0.42	0.2 percentage red blood cells Standard Error 0.46	0.2 percentage red blood cells Standard Error 0.40
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 128 (n=30, 40, 40, 30)	0.2 percentage red blood cells Standard Error 0.42	0.3 percentage red blood cells Standard Error 0.43	0.0 percentage red blood cells Standard Error 0.43	-0.1 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 141 (n=28, 39, 34, 28)	-0.1 percentage red blood cells Standard Error 0.42	-0.1 percentage red blood cells Standard Error 0.48	0.2 percentage red blood cells Standard Error 0.50	-0.2 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 154 (n=26, 34, 31, 24)	-0.8 percentage red blood cells Standard Error 0.45	-0.8 percentage red blood cells Standard Error 0.43	-1.0 percentage red blood cells Standard Error 0.51	-0.3 percentage red blood cells Standard Error 0.43
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 167 (n=24, 33, 30, 26)	-0.1 percentage red blood cells Standard Error 0.53	0.2 percentage red blood cells Standard Error 0.46	0.2 percentage red blood cells Standard Error 0.56	-0.4 percentage red blood cells Standard Error 0.48
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 180 (n=21, 28, 28, 26)	1.1 percentage red blood cells Standard Error 0.55	0.6 percentage red blood cells Standard Error 0.58	1.0 percentage red blood cells Standard Error 0.53	-0.5 percentage red blood cells Standard Error 0.57
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 193 (n=19, 26, 26, 23)	0.6 percentage red blood cells Standard Error 0.65	1.1 percentage red blood cells Standard Error 0.55	0.5 percentage red blood cells Standard Error 0.61	-0.0 percentage red blood cells Standard Error 0.59
Baseline and Changes From Baseline in Hematocrit During the ST + LT Period Change from BL at Week 206 (n=17, 22, 24, 21)	-0.4 percentage red blood cells Standard Error 0.54	0.2 percentage red blood cells Standard Error 0.52	0.2 percentage red blood cells Standard Error 0.42	-0.5 percentage red blood cells Standard Error 0.52