Trial Outcomes & Findings for Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus (TD2M) Patients (NCT NCT01020123)

NCT ID: NCT01020123

Last Updated: 2012-11-26

Results Overview

AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 530 participants
• Primary outcome timeframe: Baseline to 4th Month
• Results posted on: 2012-11-26

Participant Flow

Participant milestones

Measure	Higher Dose 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose 20 mg AZD1656 add on to metformin, fixed dose	Placebo Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Main Period STARTED	93	91	52	40	88	94	72
Main Period COMPLETED	76	77	44	33	77	83	61
Main Period NOT COMPLETED	17	14	8	7	11	11	11
Extention Period STARTED	40	35	19	13	31	38	19
Extention Period COMPLETED	37	33	17	12	31	36	18
Extention Period NOT COMPLETED	3	2	2	1	0	2	1

Reasons for withdrawal

Measure	Higher Dose 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose 20 mg AZD1656 add on to metformin, fixed dose	Placebo Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Main Period Withdrawal by Subject	6	5	3	1	6	3	2
Main Period Eligibility Criteria not fullfilled	0	1	0	0	1	0	0
Main Period Adverse Event	5	2	2	1	1	2	1
Main Period Protocol Violation	4	4	2	5	2	3	2
Main Period Lost to Follow-up	0	2	0	0	0	0	0
Main Period Unclasified	2	0	1	0	1	3	6
Extention Period Withdrawal by Subject	2	1	1	0	0	0	0
Extention Period Adverse Event	0	0	0	1	0	0	0
Extention Period Protocol Violation	1	1	1	0	0	0	1
Extention Period Lost to Follow-up	0	0	0	0	0	2	0

Baseline Characteristics

Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus (TD2M) Patients

Baseline characteristics by cohort

Measure	Higher Dose n=93 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=91 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=52 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=40 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=88 Participants Placebo add on to metformin	Glipizide n=94 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=72 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose	Total n=530 Participants Total of all reporting groups
Age Continuous	57.1 Year n=5 Participants	57.1 Year n=7 Participants	54.4 Year n=5 Participants	57.4 Year n=4 Participants	56.9 Year n=21 Participants	57.1 Year n=10 Participants	53.1 Year n=115 Participants	56 Year n=24 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	46 Participants n=7 Participants	22 Participants n=5 Participants	19 Participants n=4 Participants	45 Participants n=21 Participants	46 Participants n=10 Participants	37 Participants n=115 Participants	262 Participants n=24 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	45 Participants n=7 Participants	30 Participants n=5 Participants	21 Participants n=4 Participants	43 Participants n=21 Participants	48 Participants n=10 Participants	35 Participants n=115 Participants	268 Participants n=24 Participants

PRIMARY outcome

Timeframe: Baseline to 4th Month

Population: The population is FAS prior to rescue, using the LOCF values (see table 27 in CSR)

AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue

Outcome measures

Measure	Higher Dose n=80 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=82 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=47 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=34 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=82 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
HbA1c: Change From Baseline to 4 Month	-1.25 Percentage 95% Confidence Interval -1.14 • Interval -1.49 to -1.01	-1.26 Percentage 95% Confidence Interval -1.14 • Interval -1.49 to -1.02	-0.67 Percentage 95% Confidence Interval -0.62 • Interval -0.99 to -0.36	-0.61 Percentage 95% Confidence Interval -0.60 • Interval -0.98 to -0.24	-0.45 Percentage 95% Confidence Interval NA • Interval -0.69 to -0.21	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is FAS prior to rescue, using the LOCF values (see table 29 in CSR)

AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.

Outcome measures

Measure	Higher Dose n=90 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=87 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=49 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=39 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=85 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
FPG: to Evaluate Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue.	-0.818 mmol/L 95% Confidence Interval -1.373 • Interval -1.331 to -0.304	-1.08 mmol/L 95% Confidence Interval -1.642 • Interval -1.603 to -0.558	0.041 mmol/L 95% Confidence Interval -0.652 • Interval -0.656 to 0.738	0.024 mmol/L 95% Confidence Interval -0.737 • Interval -0.757 to 0.804	-0.182 mmol/L 95% Confidence Interval NA • Interval -0.71 to 0.347	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is FAS prior to rescue, using the LOCF values (see table 31 in CSR)

AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.

Outcome measures

Measure	Higher Dose n=58 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=63 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=38 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=26 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=57 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
SMPG: Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue.	-1.596 mmol/L 95% Confidence Interval -2.206 • Interval -2.176 to -1.016	-1.557 mmol/L 95% Confidence Interval -2.155 • Interval -2.117 to -0.997	-0.874 mmol/L 95% Confidence Interval -1.586 • Interval -1.591 to -0.157	-0.604 mmol/L 95% Confidence Interval -1.437 • Interval -1.472 to 0.265	-0.213 mmol/L 95% Confidence Interval NA • Interval -0.799 to 0.372	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is FAS prior to rescue, using the LOCF values (see table 142 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

The relative change in AUC

Outcome measures

Measure	Higher Dose n=17 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=13 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=7 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=8 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=17 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
OGTT/Plasma Glucose	0.92 ratio Interval 0.82 to 1.02	0.84 ratio Interval 0.75 to 0.96	1.02 ratio Interval 0.86 to 1.22	0.99 ratio Interval 0.84 to 1.16	0.99 ratio Interval 0.88 to 1.1	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is FAS prior to rescue, using the LOCF values (see table 146 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

The Relative Change in AUC FAS Prior to Rescue

Outcome measures

Measure	Higher Dose n=16 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=12 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=6 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=10 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=16 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
OGTT/Insulin	0.81 ratio Interval 0.66 to 0.99	1.08 ratio Interval 0.85 to 1.36	0.97 ratio Interval 0.69 to 1.35	0.90 ratio Interval 0.69 to 1.16	0.91 ratio Interval 0.74 to 1.12	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is FAS prior to rescue, using the LOCF values (see table 150 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

The relative change, FAS prior to rescue

Outcome measures

Measure	Higher Dose n=17 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=13 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=7 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=10 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=16 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
OGTT/C-peptide	0.97 ratio Interval 0.85 to 1.1	1.11 ratio Interval 0.96 to 1.29	0.90 ratio Interval 0.74 to 1.1	0.95 ratio Interval 0.81 to 1.13	1.00 ratio Interval 0.87 to 1.14	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is FAS prior to rescue, using the LOCF values (see table 154 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

The relative change, FAS prior to rescue

Outcome measures

Measure	Higher Dose n=16 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=12 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=6 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=10 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=14 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
OGTT/Pro-insulin/Insulin	1.496 Ratio Interval 1.25 to 1.791	1.199 Ratio Interval 0.973 to 1.476	1.248 Ratio Interval 0.932 to 1.672	1.431 Ratio Interval 1.135 to 1.805	1.185 Ratio Interval 0.979 to 1.436	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is FAS prior to rescue, using the observed cases (see table 35 in CSR).

Number of responders ≤ 7, FAS prior to rescue.

Outcome measures

Measure	Higher Dose n=74 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=73 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=38 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=69 Participants Placebo add on to metformin	Glipizide n=78 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=48 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
HbA1c ≤ 7	43 Participants	43 Participants	14 Participants	11 Participants	16 Participants	50 Participants	24 Participants

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 228 in CSR).

Number of Responders ≤ 6.5, FAS Prior to Rescue

Outcome measures

Measure	Higher Dose n=74 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=73 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=38 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=69 Participants Placebo add on to metformin	Glipizide n=78 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=48 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
HbA1c ≤ 6.5	35 Participants	27 Participants	9 Participants	4 Participants	9 Participants	30 Participants	16 Participants

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 228 in CSR)

Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.

Outcome measures

Measure	Higher Dose n=74 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=75 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=73 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
LDL-C: Mean Ratio	1.07 ratio 95% Confidence Interval 29.5 • Interval 1.01 to 1.13	1.02 ratio 95% Confidence Interval 20.6 • Interval 0.97 to 1.08	1.07 ratio 95% Confidence Interval 38.5 • Interval 0.99 to 1.15	1.04 ratio 95% Confidence Interval 23.1 • Interval 0.96 to 1.13	1.02 ratio 95% Confidence Interval 19.3 • Interval 0.97 to 1.08	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 230 in CSR)

Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=76 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=74 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
HDL-C: Change From Baseline	1.06 ratio 95% Confidence Interval 6.2 • Interval 1.02 to 1.09	1.06 ratio 95% Confidence Interval 5.1 • Interval 1.03 to 1.1	1.05 ratio 95% Confidence Interval 7.8 • Interval 1.01 to 1.09	1.03 ratio 95% Confidence Interval 4.1 • Interval 0.99 to 1.08	1.03 ratio 95% Confidence Interval 5.3 • Interval 1.0 to 1.06	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 232 in CSR)

Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=76 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=74 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Total Cholesterol: Change From Baseline	1.09 ratio 95% Confidence Interval 36.9 • Interval 1.04 to 1.13	1.08 ratio 95% Confidence Interval 60.2 • Interval 1.04 to 1.12	1.07 ratio 95% Confidence Interval 41.6 • Interval 1.02 to 1.13	1.04 ratio 95% Confidence Interval 25.3 • Interval 0.98 to 1.1	1.03 ratio 95% Confidence Interval 26.0 • Interval 0.99 to 1.07	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 226 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=75 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=74 Participants Placebo add on to metformin	Glipizide n=82 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=58 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Triglycerides: Change From Baseline	40.9 mg/dL Standard Deviation 115.3 • Interval 39.2 to 114.4	38.7 mg/dL Standard Deviation 99.3 • Interval 38.7 to 99.3	19.8 mg/dL Standard Deviation 185.3 • Interval 19.8 to 185.3	4.4 mg/dL Standard Deviation 49.3 • Interval 4.4 to 49.3	13.7 mg/dL Standard Deviation 139.4 • Interval 13.4 to 139.4	18.7 mg/dL Standard Deviation 152.8 • Interval 13.7 to 139.4	29.8 mg/dL Standard Deviation 174.3 • Interval 18.7 to 152.8

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 234 in CSR)

Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=76 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=75 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
C-reactive Protein: Change From Baseline	0.30 ratio 95% Confidence Interval 0.88 • Interval 0.08 to 0.52	0.08 ratio 95% Confidence Interval 0.86 • Interval -0.14 to 0.3	0.09 ratio 95% Confidence Interval 0.99 • Interval -0.2 to 0.3	0.06 ratio 95% Confidence Interval 0.74 • Interval -0.4 to 0.27	-0.02 ratio 95% Confidence Interval 0.75 • Interval -0.24 to 0.2	—	—

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 237 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=73 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=38 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=69 Participants Placebo add on to metformin	Glipizide n=79 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=58 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Systolic Blood Pressure, Change From Baseline	-0.4 mmHg Standard Deviation 12.6	0.4 mmHg Standard Deviation 9.9	5.7 mmHg Standard Deviation 11.3	0.1 mmHg Standard Deviation 12.6	-0.2 mmHg Standard Deviation 13.7	-1.1 mmHg Standard Deviation 13.5	-0.3 mmHg Standard Deviation 11.7

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 240 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=73 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=38 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=69 Participants Placebo add on to metformin	Glipizide n=79 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=58 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Diastolic Blood Pressure, Change From Baseline	1.1 mmHg Standard Deviation 8.6	1.4 mmHg Standard Deviation 8.5	1.3 mmHg Standard Deviation 9.1	-0.9 mmHg Standard Deviation 10.8	-0.3 mmHg Standard Deviation 8.5	-0.1 mmHg Standard Deviation 7.2	0.5 mmHg Standard Deviation 7.7

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 236 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=73 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=38 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=69 Participants Placebo add on to metformin	Glipizide n=79 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=58 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Pulse, Change From Baseline	0.4 Beats/min Standard Deviation 8.8	1.6 Beats/min Standard Deviation 7.9	1.3 Beats/min Standard Deviation 7.9	0.3 Beats/min Standard Deviation 9.1	-1.1 Beats/min Standard Deviation 9.4	-0.4 Beats/min Standard Deviation 11.6	1.3 Beats/min Standard Deviation 8.5

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 244 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=73 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=38 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=69 Participants Placebo add on to metformin	Glipizide n=79 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=48 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Weight, Change From Baseline	-0.3 kg Standard Deviation 2.5	-0.6 kg Standard Deviation 2.9	-1.2 kg Standard Deviation 2.7	-1.4 kg Standard Deviation 2.3	-1.0 kg Standard Deviation 2.5	1.0 kg Standard Deviation 3.4	-0.4 kg Standard Deviation 4.4

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 258 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=74 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=76 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=34 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=77 Participants Placebo add on to metformin	Glipizide n=83 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=63 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
QTcF; Electorcardiagram Change From Baseline	4.4 msec Standard Deviation 15.6	4.0 msec Standard Deviation 14.5	-2.6 msec Standard Deviation 12.6	3.8 msec Standard Deviation 17.9	2.2 msec Standard Deviation 13.8	2.7 msec Standard Deviation 21.5	1.6 msec Standard Deviation 16.4

SECONDARY outcome

Timeframe: baseline to 4 month

Population: population is safety analysis set regardless of rescue, using the observed cases (see table 197 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=76 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=77 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=44 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=76 Participants Placebo add on to metformin	Glipizide n=83 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=61 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Haemoglobin; Change From Baseline	-0.20 g/dL Standard Deviation 0.68	-0.18 g/dL Standard Deviation 0.62	0.00 g/dL Standard Deviation 0.63	-0.11 g/dL Standard Deviation 0.69	-0.20 g/dL Standard Deviation 0.71	0.02 g/dL Standard Deviation 0.69	-0.25 g/dL Standard Deviation 0.76

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 198 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=76 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=77 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=44 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=76 Participants Placebo add on to metformin	Glipizide n=83 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=61 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Leukocytes; Change From Baseline	0.39 *10^3 cells/µL Standard Deviation 1.29	0.34 *10^3 cells/µL Standard Deviation 1.59	0.35 *10^3 cells/µL Standard Deviation 1.41	-0.15 *10^3 cells/µL Standard Deviation 1.09	-0.8 *10^3 cells/µL Standard Deviation 1.09	0.27 *10^3 cells/µL Standard Deviation 1.43	-40 *10^3 cells/µL Standard Deviation 1.31

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 215 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=77 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=44 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=76 Participants Placebo add on to metformin	Glipizide n=83 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=60 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Sodium; Change From Baseline	-0.6 mEq/L Standard Deviation 2.4	-0.7 mEq/L Standard Deviation 2.4	-0.4 mEq/L Standard Deviation 3.0	-0.1 mEq/L Standard Deviation 2.6	0.0 mEq/L Standard Deviation 2.6	-0.6 mEq/L Standard Deviation 3.3	0.5 mEq/L Standard Deviation 2.6

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 214 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=77 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=75 Participants Placebo add on to metformin	Glipizide n=82 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=58 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Potassium; Change From Baseline	0.02 mEq/L Standard Deviation 0.45	-0.02 mEq/L Standard Deviation 0.26	0.00 mEq/L Standard Deviation 0.35	-0.01 mEq/L Standard Deviation 0.29	-0.02 mEq/L Standard Deviation 0.34	0.07 mEq/L Standard Deviation 0.39	0.05 mEq/L Standard Deviation 0.38

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 211 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=77 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=75 Participants Placebo add on to metformin	Glipizide n=82 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=59 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Creatinine; Change From Baseline	0.4 IU/L Standard Deviation 70.5	-9.9 IU/L Standard Deviation 87.8	8.5 IU/L Standard Deviation 88.7	-8.3 IU/L Standard Deviation 39.1	-0.1 IU/L Standard Deviation 32.2	15.9 IU/L Standard Deviation 67.1	-7.3 IU/L Standard Deviation 47

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 206 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=76 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=75 Participants Placebo add on to metformin	Glipizide n=82 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=59 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
ALT; Change From Baseline	2.0 IU/L Standard Deviation 12.0	1.7 IU/L Standard Deviation 14.8	3.2 IU/L Standard Deviation 17.7	-1.8 IU/L Standard Deviation -1.8	-0.4 IU/L Standard Deviation 11.3	2.0 IU/L Standard Deviation 15.3	-0.4 IU/L Standard Deviation 15.5

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 207 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=76 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=43 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=32 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=75 Participants Placebo add on to metformin	Glipizide n=82 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=59 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
AST; Change From Baseline	2.4 IU/L Standard Deviation 9.8	2.0 IU/L Standard Deviation 11.0	2.8 IU/L Standard Deviation 13.1	-0.6 IU/L Standard Deviation 8.9	-0.1 IU/L Standard Deviation 7.9	2.1 IU/L Standard Deviation 13.3	2.7 IU/L Standard Deviation 9.6

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 208 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=77 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=44 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=76 Participants Placebo add on to metformin	Glipizide n=83 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=59 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Alkaline Phosphatase; Change From Baseline	3.8 IU/L Standard Deviation 17.5	-1.3 IU/L Standard Deviation 13.3	0.0 IU/L Standard Deviation 13.6	-1.8 IU/L Standard Deviation 11.9	-3.4 IU/L Standard Deviation 11.5	-4.2 IU/L Standard Deviation 16.7	-11.7 IU/L Standard Deviation 24.7

SECONDARY outcome

Timeframe: baseline to 4 month

Population: The population is safety analysis set regardless of rescue, using the observed cases (see table 209 in CSR)

Summary statistic of change from baseline

Outcome measures

Measure	Higher Dose n=75 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=77 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=44 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=33 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=76 Participants Placebo add on to metformin	Glipizide n=83 Participants 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=59 Participants Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Bilirubin; Change From Baseline	-0.02 mg/dL Standard Deviation 0.17	-0.06 mg/dL Standard Deviation 0.21	0.02 mg/dL Standard Deviation 0.13	-0.05 mg/dL Standard Deviation 0.20	-0.01 mg/dL Standard Deviation 0.20	-0.07 mg/dL Standard Deviation 0.20	-11.7 mg/dL Standard Deviation 24.7

SECONDARY outcome

Timeframe: at 4 month

The value is calculated using an allometric model (of a patient weighting 75 kg). The value is independent treatment given.

Outcome measures

Measure	Higher Dose n=86 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=87 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=49 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=39 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=70 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
CL/F to Characterise the PK Properties of AZD1656.	9.29 L/h Standard Error 3.7	9.29 L/h Standard Error 3.7	9.29 L/h Standard Error 3.7	9.29 L/h Standard Error 3.7	9.29 L/h Standard Error 3.7	—	—

SECONDARY outcome

Timeframe: at 4 month

The value is model based. The value is independent treatment given.

Outcome measures

Measure	Higher Dose n=86 Participants 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=87 Participants 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=49 Participants 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=39 Participants 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=70 Participants Placebo add on to metformin	Glipizide 5-20 mg Glipizide add on to metformin, titrated dose	Open Label Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
EC50 to Characterise the PD Properties of AZD1656.	60.2 nmol/L Standard Error 14	60.2 nmol/L Standard Error 14	60.1 nmol/L Standard Error 14	60.2 nmol/L Standard Error 14	60.2 nmol/L Standard Error 14	—	—

Adverse Events

Higher Dose

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Lower Dose

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

40 mg Fixed Dose

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

20 mg Fixed Dose

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Glipizide

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Open Label

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Higher Dose n=92 participants at risk 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=90 participants at risk 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=50 participants at risk 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=40 participants at risk 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=87 participants at risk Placebo add on to metformin	Glipizide n=93 participants at risk 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=71 participants at risk Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Investigations Blood Creatine Phosphokinase Increased	1.1% 1/92 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Cardiac disorders Angina Unstable	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	2.5% 1/40 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Nervous system disorders Cerebrovascular accident	1.1% 1/92 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Metabolism and nutrition disorders Diabetic foot	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/90 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	2.0% 1/50 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Vascular disorders Hypertensive emergency	1.1% 1/92 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Cardiac disorders Acute myocardial infarction	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/93 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Infections and infestations Anal abscess	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	1.4% 1/71 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month
Cardiac disorders Angina pectoris	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/93 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/93 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Renal and urinary disorders Renal failur acute	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/87 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/87 • Number of events 1 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month

Other adverse events

Measure	Higher Dose n=92 participants at risk 20-200 mg AZD1656 add on to metformin, titrated dose	Lower Dose n=90 participants at risk 10-140 mg AZD1656 add on to metformin, titrated dose	40 mg Fixed Dose n=50 participants at risk 40 mg AZD1656 add on to metformin, fixed dose	20 mg Fixed Dose n=40 participants at risk 20 mg AZD1656 add on to metformin, fixed dose	Placebo n=87 participants at risk Placebo add on to metformin	Glipizide n=93 participants at risk 5-20 mg Glipizide add on to metformin, titrated dose	Open Label n=71 participants at risk Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Skin and subcutaneous tissue disorders Hyperhidrosis	1.1% 1/92 • Baseline - 6 month Safety was collected in 6 month	4.4% 4/90 • Baseline - 6 month Safety was collected in 6 month	2.0% 1/50 • Baseline - 6 month Safety was collected in 6 month	2.5% 1/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	10.8% 10/93 • Baseline - 6 month Safety was collected in 6 month	2.8% 2/71 • Baseline - 6 month Safety was collected in 6 month
Infections and infestations Nasopharyngitis	4.3% 4/92 • Baseline - 6 month Safety was collected in 6 month	10.0% 9/90 • Baseline - 6 month Safety was collected in 6 month	4.0% 2/50 • Baseline - 6 month Safety was collected in 6 month	2.5% 1/40 • Baseline - 6 month Safety was collected in 6 month	6.9% 6/87 • Baseline - 6 month Safety was collected in 6 month	3.2% 3/93 • Baseline - 6 month Safety was collected in 6 month	4.2% 3/71 • Baseline - 6 month Safety was collected in 6 month
Infections and infestations Gastroenteritis	2.2% 2/92 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/90 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/50 • Baseline - 6 month Safety was collected in 6 month	5.0% 2/40 • Baseline - 6 month Safety was collected in 6 month	2.3% 2/87 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Gastrointestinal disorders Diarrhoea	4.3% 4/92 • Baseline - 6 month Safety was collected in 6 month	7.8% 7/90 • Baseline - 6 month Safety was collected in 6 month	6.0% 3/50 • Baseline - 6 month Safety was collected in 6 month	7.5% 3/40 • Baseline - 6 month Safety was collected in 6 month	3.4% 3/87 • Baseline - 6 month Safety was collected in 6 month	3.2% 3/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Gastrointestinal disorders Nausea	2.2% 2/92 • Baseline - 6 month Safety was collected in 6 month	2.2% 2/90 • Baseline - 6 month Safety was collected in 6 month	8.0% 4/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/87 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/93 • Baseline - 6 month Safety was collected in 6 month	1.4% 1/71 • Baseline - 6 month Safety was collected in 6 month
Gastrointestinal disorders Vomiting	0.00% 0/92 • Baseline - 6 month Safety was collected in 6 month	2.2% 2/90 • Baseline - 6 month Safety was collected in 6 month	10.0% 5/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Gastrointestinal disorders Gastritis	1.1% 1/92 • Baseline - 6 month Safety was collected in 6 month	1.1% 1/90 • Baseline - 6 month Safety was collected in 6 month	2.0% 1/50 • Baseline - 6 month Safety was collected in 6 month	5.0% 2/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	2.2% 2/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
General disorders Asthenia	2.2% 2/92 • Baseline - 6 month Safety was collected in 6 month	4.4% 4/90 • Baseline - 6 month Safety was collected in 6 month	2.0% 1/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	7.5% 7/93 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/71 • Baseline - 6 month Safety was collected in 6 month
Nervous system disorders Tremor	4.3% 4/92 • Baseline - 6 month Safety was collected in 6 month	4.4% 4/90 • Baseline - 6 month Safety was collected in 6 month	2.0% 1/50 • Baseline - 6 month Safety was collected in 6 month	2.5% 1/40 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/87 • Baseline - 6 month Safety was collected in 6 month	10.8% 10/93 • Baseline - 6 month Safety was collected in 6 month	1.4% 1/71 • Baseline - 6 month Safety was collected in 6 month
Nervous system disorders Dizziness	2.2% 2/92 • Baseline - 6 month Safety was collected in 6 month	3.3% 3/90 • Baseline - 6 month Safety was collected in 6 month	4.0% 2/50 • Baseline - 6 month Safety was collected in 6 month	0.00% 0/40 • Baseline - 6 month Safety was collected in 6 month	2.3% 2/87 • Baseline - 6 month Safety was collected in 6 month	6.5% 6/93 • Baseline - 6 month Safety was collected in 6 month	2.8% 2/71 • Baseline - 6 month Safety was collected in 6 month

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60